Is DNAH3 p.Val2495= (c.7485T>G) pathogenic?

DNAH3 p.Val2495= (c.7485T>G) is classified Benign in DNAH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-14). Rare (popmax 0.686%, eas).

How common is DNAH3 p.Val2495= (c.7485T>G) in the general population?

DNAH3 p.Val2495= (c.7485T>G) is rare (popmax 0.686%, eas) (gnomAD).

DNAH3 p.Val2495=

c.7485T>G · rs144003723 · VCV708193

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.686%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP -20	GERP -5
Overall
CADD	0.003	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.686% East Asian · 308/44,884 alleles

Filtering AF 0.623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.598%

Overall 0.025% 403/1,614,144 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.686%	146
South Asian	0.0747%	1,339
Remaining individualsnot grpmax-eligible	0.0336%	2,977
European (non-Finnish)	0.000508%	196,666

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.Val2495=
Coding: c.7485T>G
MANE Select: NM_001347886
dbSNP: rs144003723
Type: single nucleotide variant
Location: chr16:20985119 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Residue 2495: 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 4' 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-val2495 (accessed [today's date]).

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