Is DNAH2 p.Ala316Val (c.947C>T) pathogenic?

DNAH2 p.Ala316Val (c.947C>T) is classified Likely benign in DNAH2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-17). AlphaMissense: likely benign (0.0797); Rare (popmax 0.68%, afr); Associated with DNAH2-related disorder.

What condition is associated with DNAH2 p.Ala316Val (c.947C>T)?

DNAH2 p.Ala316Val (c.947C>T) is associated with DNAH2-related disorder (ClinVar).

How common is DNAH2 p.Ala316Val (c.947C>T) in the general population?

DNAH2 p.Ala316Val (c.947C>T) is rare (popmax 0.68%, afr) (gnomAD).

What do computational predictors say about DNAH2 p.Ala316Val (c.947C>T)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

DNAH2 p.Ala316Val

c.947C>T · rs140392785 · VCV3033250

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.68%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

DNAH2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.14	moderately 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 0.26	GERP 0.044
Regional constraint	o/e 0.88	unconstrained · MANE · 73 kb · p 9.6e-12 · regional, not allelic
Overall
CADD	11.84	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 0.68% African / African-American · 507/74,574 alleles

Filtering AF 0.631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.612%

Overall 0.0352% 567/1,612,616 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.68%	147
Remaining individualsnot grpmax-eligible	0.0352%	2,840
Admixed American	0.0318%	3,142
Middle Eastern	0.0165%	6,060
East Asian	0.0067%	14,931
South Asian	0.00661%	15,134
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594
European (non-Finnish)	0.000678%	147,480

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.Ala316Val
Coding: c.947C>T
MANE Select: NM_020877
dbSNP: rs140392785
Type: single nucleotide variant
Location: chr17:7734677 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI <0.01 (gnomAD)
Residue 316: the 'stem' region

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

Disease context

DNAH2-related disorder

Similar variants

DNAH2 p.Ala316= Benign same residue
DNAH2 p.Arg1633Gly Uncertain significance ⚠ same condition
DNAH2 c.11478+4G>A Benign same condition
DNAH2 c.1171-715G>A Likely benign same condition
DNAH2 c.1377-9C>A Likely benign same condition
DNAH2 c.1904+123T>C Benign same condition
DNAH2 c.1904+136C>T Likely benign same condition
DNAH2 c.1904+345A>G 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-ala316val (accessed [today's date]).

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