Is DNAH3 p.Ala3373Thr (c.10117G>A) pathogenic?

DNAH3 p.Ala3373Thr (c.10117G>A) is classified Uncertain significance in DNAH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely benign (0.1482); Ultra-rare (popmax 0.0168%, nfe).

How common is DNAH3 p.Ala3373Thr (c.10117G>A) in the general population?

DNAH3 p.Ala3373Thr (c.10117G>A) is ultra-rare (popmax 0.0168%, nfe) (gnomAD).

What do computational predictors say about DNAH3 p.Ala3373Thr (c.10117G>A)?

AlphaMissense predicts likely benign (score 0.1482) — an in-silico prediction, not a clinical call.

DNAH3 p.Ala3373Thr

c.10117G>A · rs769116142 · VCV2391702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1482 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0168%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1482	likely benign
REVEL	0.215	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 0.91	GERP -0.54, phastCons 0.99
Overall
CADD	14.53	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 A3419T vs ClinVar A3373T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0168% European (non-Finnish) · 198/1,180,008 alleles

Filtering AF 0.0149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0141%

Overall 0.0126% 204/1,613,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0168%	5,960
Remaining individualsnot grpmax-eligible	0.008%	12,497
African / African-American	0.00134%	74,872

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.Ala3373Thr
Coding: c.10117G>A
MANE Select: NM_001347886
dbSNP: rs769116142
Type: single nucleotide variant
Location: chr16:20963629 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Residue 3373: 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)

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-ala3373thr (accessed [today's date]).

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