Is DNAH3 p.Ala1097= (c.3291A>C) pathogenic?

DNAH3 p.Ala1097= (c.3291A>C) is classified Benign in DNAH3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2016-03-29). Common (popmax 70.4%, eas) — too common for a highly-penetrant pathogenic allele.

DNAH3 p.Ala1097=

Q: How common is DNAH3 p.Ala1097= (c.3291A>C) in the general population?

DNAH3 p.Ala1097= (c.3291A>C) is common (popmax 70.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3291A>C · rs861424 · VCV402724

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 70.4%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -4.7
Overall
CADD	3.774	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 70.4% East Asian · 31,575/44,822 alleles

Filtering AF 69.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 69.5%

Overall 42.3% 682,738/1,613,456 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	70.4%	1
Admixed American	46.4%	2
Finnishnot grpmax-eligible	46%	2
South Asian	45%	2
Ashkenazi Jewishnot grpmax-eligible	44.3%	2
Remaining individualsnot grpmax-eligible	42.7%	2
Amishnot grpmax-eligible	42.5%	2
European (non-Finnish)	41%	2
Middle Eastern	39.1%	3
African / African-American	36.5%	3

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.Ala1097=
Coding: c.3291A>C
MANE Select: NM_001347886
dbSNP: rs861424
Type: single nucleotide variant
Location: chr16:21067372 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Residue 1097: the 'stem' region; 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)

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-ala1097 (accessed [today's date]).

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