Is DNAI2 p.Asp554His (c.1660G>C) pathogenic?

DNAI2 p.Asp554His (c.1660G>C) is classified Uncertain significance in DNAI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-30). AlphaMissense: likely benign (0.1367); Absent from gnomAD v4.1; Associated with primary ciliary dyskinesia.

What condition is associated with DNAI2 p.Asp554His (c.1660G>C)?

DNAI2 p.Asp554His (c.1660G>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAI2 p.Asp554His (c.1660G>C) in the general population?

DNAI2 p.Asp554His (c.1660G>C) is absent from gnomAD v4.1 (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.Asp554His (c.1660G>C)?

AlphaMissense predicts likely benign (score 0.1367) — an in-silico prediction, not a clinical call.

DNAI2 p.Asp554His

c.1660G>C · rs117932646 · VCV408969

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1367 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.1367	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -8.58	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 0.032	GERP -2.1
Regional constraint	o/e 0.86	unconstrained · MANE · 32 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	13.34	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAI2
Protein: p.Asp554His
Coding: c.1660G>C
MANE Select: NM_023036
dbSNP: rs117932646
Type: single nucleotide variant
Location: chr17:74312168 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

DNAI2 p.Asp554Asn Benign/Likely benign ★★ same residue
DNAI2 p.Asp554= Likely benign ★ same residue
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

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-asp554his (accessed [today's date]).

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