Is DNAH2 p.Pro1605Ser (c.4813C>T) pathogenic?

DNAH2 p.Pro1605Ser (c.4813C>T) is classified Conflicting classifications of pathogenicity in DNAH2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-12). AlphaMissense: likely benign (0.2128); Rare (popmax 0.28%, afr); Associated with Inborn genetic diseases.

What condition is associated with DNAH2 p.Pro1605Ser (c.4813C>T)?

DNAH2 p.Pro1605Ser (c.4813C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAH2 p.Pro1605Ser (c.4813C>T) in the general population?

DNAH2 p.Pro1605Ser (c.4813C>T) is rare (popmax 0.28%, afr) (gnomAD).

What do computational predictors say about DNAH2 p.Pro1605Ser (c.4813C>T)?

AlphaMissense predicts likely benign (score 0.2128) — an in-silico prediction, not a clinical call.

DNAH2 p.Pro1605Ser

c.4813C>T · rs150496167 · VCV715312

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2128 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.28%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2128	likely benign
REVEL	0.28	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.5, phastCons 0.99
Regional constraint	o/e 0.88	unconstrained · MANE · 73 kb · p 9.6e-12 · regional, not allelic
Overall
CADD	18.61	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 0.28% African / African-American · 210/74,888 alleles

Filtering AF 0.249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.237%

Overall 0.015% 242/1,610,800 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.28%	357
Remaining individualsnot grpmax-eligible	0.0289%	3,463
Admixed American	0.0167%	5,975
South Asian	0.00221%	45,191
European (non-Finnish)	0.00017%	589,213

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: DNAH2
Protein: p.Pro1605Ser
Coding: c.4813C>T
MANE Select: NM_020877
dbSNP: rs150496167
Type: single nucleotide variant
Location: chr17:7775334 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 1605: the 'stem' region

Full DNAH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAH2 p.Ala1036Val Uncertain significance ★★ ⚠ same condition
DNAH2 p.Arg1533Cys Uncertain significance ★★ ⚠ same condition
DNAH2 p.Arg2538Gln Uncertain significance ★★ same condition
DNAH2 p.Arg3759His Uncertain significance ★★ ⚠ same condition
DNAH2 p.Gln2069Glu Uncertain significance ★★ same condition
DNAH2 p.Ile4043Ser Uncertain significance ★★ ⚠ same condition
DNAH2 p.Pro3819Leu Uncertain significance ★★ ⚠ same condition
DNAH2 p.Ala1058Thr Benign/Likely benign ★★ 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/dnah2-p-pro1605ser (accessed [today's date]).

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