Is DNAH5 p.Pro2717Ser (c.8149C>T) pathogenic?

DNAH5 p.Pro2717Ser (c.8149C>T) is classified Likely benign in DNAH5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-19). AlphaMissense: likely pathogenic (0.8374); Very rare (popmax 0.00401%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Pro2717Ser (c.8149C>T)?

DNAH5 p.Pro2717Ser (c.8149C>T) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH5 p.Pro2717Ser (c.8149C>T) in the general population?

DNAH5 p.Pro2717Ser (c.8149C>T) is very rare (popmax 0.00401%, afr) (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 DNAH5 p.Pro2717Ser (c.8149C>T)?

AlphaMissense predicts likely pathogenic (score 0.8374) — an in-silico prediction, not a clinical call.

DNAH5 p.Pro2717Ser

c.8149C>T · rs779628660 · VCV2721155

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8374 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.8374	likely pathogenic
REVEL	0.431	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 2.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 228 kb · p 0.16 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,900 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00031% 5/1,613,992 alleles · very rare exomes 4/1,461,876 · genomes 1/152,116 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,967
Admixed American	0.00167%	59,994
European (non-Finnish)	8.47e-05%	1,180,016

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: DNAH5
Protein: p.Pro2717Ser
Coding: c.8149C>T
MANE Select: NM_001369
dbSNP: rs779628660
Type: single nucleotide variant
Location: chr5:13793590 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2717: the 'aaa 3' region

Full DNAH5 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

DNAH5 p.Pro2717= Likely benign ★ same residue
DNAH5 c.10555+1G>C Likely pathogenic ★★ same condition
DNAH5 c.1089+1G>A Pathogenic ★★ same condition
DNAH5 c.11028+2T>C Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11029-2A>T Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11571-1G>A Pathogenic ★★ same condition
DNAH5 c.12910-1G>C Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.1320+1G>A 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/dnah5-p-pro2717ser (accessed [today's date]).

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