Is DNAH3 p.Ala3052Val (c.9155C>T) pathogenic?

DNAH3 p.Ala3052Val (c.9155C>T) is classified Uncertain significance in DNAH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: likely benign (0.083); Ultra-rare (popmax 0.015%, amr).

How common is DNAH3 p.Ala3052Val (c.9155C>T) in the general population?

DNAH3 p.Ala3052Val (c.9155C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about DNAH3 p.Ala3052Val (c.9155C>T)?

AlphaMissense predicts likely benign (score 0.083) — an in-silico prediction, not a clinical call.

DNAH3 p.Ala3052Val

c.9155C>T · rs139282400 · VCV2212878

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.083 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.083	likely benign
REVEL	0.015	strongly 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 0.086	GERP -4.6
Overall
CADD	8.984	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A3098V vs ClinVar A3052V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/59,994 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00595% 96/1,613,992 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,666
African / African-American	0.00935%	10,697
Finnishnot grpmax-eligible	0.00625%	16,006
European (non-Finnish)	0.00602%	16,620
Remaining individualsnot grpmax-eligible	0.0048%	20,828
South Asian	0.0022%	45,543

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: DNAH3
Protein: p.Ala3052Val
Coding: c.9155C>T
MANE Select: NM_001347886
dbSNP: rs139282400
Type: single nucleotide variant
Location: chr16:20964591 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Residue 3052: a UniProt-annotated variant site (found in a male with oligoasthenoteratozoospermia; uncertain significance; severely impaired sperm motility; multiple morphological abnormalities of the sperm flagella; partial loss and disintegration of the flagellar axoneme, accompanied by damage to the mitochondrial sheath); a UniProt-annotated variant site (found in a male with asthenoteratozoospermia; uncertain significance; severely impaired sperm motility; multiple morphological abnormalities of the sperm flagella; disorganization of flagellar components, notably inner dynein arms); the 'aaa 5' region

Full DNAH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH3 p.Ala1918Gly Uncertain significance ★★ ⚠ same type
DNAH3 p.Arg1228Gln Uncertain significance ★★ same type
DNAH3 p.Arg635Gln Uncertain significance ★★ same type
DNAH3 p.Asn1728Ser Uncertain significance ★★ ⚠ same type
DNAH3 p.Asp3656Asn Uncertain significance ★★ same type
DNAH3 p.Leu2597Val Uncertain significance ★★ same type
DNAH3 p.Leu4044Phe Uncertain significance ★★ ⚠ same type
DNAH3 p.Lys374Gln Uncertain significance ★★ ⚠ same type

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/dnah3-p-ala3052val (accessed [today's date]).

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