Is DNAH3 p.Arg3434Gln (c.10301G>A) pathogenic?

DNAH3 p.Arg3434Gln (c.10301G>A) is classified Likely pathogenic in DNAH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-26). AlphaMissense: likely pathogenic (0.829); Ultra-rare (popmax 0.0406%, sas); Associated with spermatogenic failure 18.

What condition is associated with DNAH3 p.Arg3434Gln (c.10301G>A)?

DNAH3 p.Arg3434Gln (c.10301G>A) is associated with spermatogenic failure 18 (ClinVar).

How common is DNAH3 p.Arg3434Gln (c.10301G>A) in the general population?

DNAH3 p.Arg3434Gln (c.10301G>A) is ultra-rare (popmax 0.0406%, sas) (gnomAD).

What do computational predictors say about DNAH3 p.Arg3434Gln (c.10301G>A)?

AlphaMissense predicts likely pathogenic (score 0.829) — an in-silico prediction, not a clinical call.

DNAH3 p.Arg3434Gln

c.10301G>A · rs776237346 · VCV2627625

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.829 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0406%, sas)

Conditions

spermatogenic failure 18

Computational evidence

Protein change
AlphaMissense	0.829	likely pathogenic ✓ concordant with ClinVar
REVEL	0.569	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R3480Q vs ClinVar R3434Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0406% South Asian · 37/91,086 alleles

Filtering AF 0.0303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0267%

Overall 0.00465% 75/1,614,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0406%	2,462
East Asian	0.0178%	5,609
African / African-American	0.00533%	18,753
Admixed American	0.005%	20,001
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	0.00169%	59,001

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.Arg3434Gln
Coding: c.10301G>A
MANE Select: NM_001347886
dbSNP: rs776237346
Type: single nucleotide variant
Location: chr16:20963445 (GRCh38)
Gene constraint: LOEUF 0.834 · pLI <0.01 (gnomAD)
Residue 3434: 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); a UniProt-annotated variant site (found in a male with oligoasthenoteratozoospermia; uncertain significance; severely impaired sperm motility; multiple morphological abnormalities of the sperm flagella; disorganization of the flagellar axoneme ultrastructure, including abnormalities in the inner dynein arms, mitochondrial sheath and fibrous sheath)

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

Disease context

spermatogenic failure 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAH3 p.Arg3434Trp Uncertain significance ★ ⚠ same residue
DNAH3 p.Gly1669Ser Pathogenic ★ same condition
DNAH3 p.Phe2279Leu Likely pathogenic ★ same condition
DNAH3 p.Trp3374Ter Likely pathogenic ★ same condition
DNAH3 p.Arg2945Cys Conflicting classifications of pathogenicity ★ same condition
DNAH3 p.Asp2447Asn Conflicting classifications of pathogenicity ★ same condition
DNAH3 p.Ala1918Gly Uncertain significance ★★ ⚠ same type
DNAH3 p.Arg1228Gln 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-arg3434gln (accessed [today's date]).

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