Is DNAI2 p.Pro191Ser (c.571C>T) pathogenic?

DNAI2 p.Pro191Ser (c.571C>T) is classified Conflicting classifications of pathogenicity in DNAI2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-12-20). AlphaMissense: likely benign (0.1035); Ultra-rare (popmax 0.0164%, mid); Associated with primary ciliary dyskinesia 9.

What condition is associated with DNAI2 p.Pro191Ser (c.571C>T)?

DNAI2 p.Pro191Ser (c.571C>T) is associated with primary ciliary dyskinesia 9, primary ciliary dyskinesia (ClinVar).

How common is DNAI2 p.Pro191Ser (c.571C>T) in the general population?

DNAI2 p.Pro191Ser (c.571C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DNAI2 p.Pro191Ser (c.571C>T)?

AlphaMissense predicts likely benign (score 0.1035) — an in-silico prediction, not a clinical call.

DNAI2 p.Pro191Ser

c.571C>T · rs201457010 · VCV228613

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1035 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 9

Computational evidence

Protein change
AlphaMissense	0.1035	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -9.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 32 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	17.09	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.0195% 314/1,613,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.368%	272
Remaining individualsnot grpmax-eligible	0.0288%	3,471
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.0153%	6,519
African / African-American	0.00267%	37,428
East Asian	0.00223%	44,868
Admixed American	0.00167%	59,960
Finnishnot grpmax-eligible	0.00156%	64,004

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DNAI2
Protein: p.Pro191Ser
Coding: c.571C>T
MANE Select: NM_023036
dbSNP: rs201457010
Type: single nucleotide variant
Location: chr17:74289697 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 84.27 · 1 PDB

Full DNAI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAI2 c.1348-1G>A Likely pathogenic ★★ same condition
DNAI2 c.1494+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAI2 c.1494+1G>T Pathogenic/Likely pathogenic ★★ same condition
DNAI2 c.1495-2A>T Likely pathogenic ★★ same condition
DNAI2 c.346-3T>G Pathogenic/Likely pathogenic ★★ same condition
DNAI2 c.610+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAI2 c.610+1G>T Likely pathogenic ★★ same condition
DNAI2 c.725-2A>C Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dnai2-p-pro191ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown