Is DNAH1 p.Ala3685= (c.11055C>T) pathogenic?

DNAH1 p.Ala3685= (c.11055C>T) is classified Benign/Likely benign in DNAH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-01). Rare (popmax 0.408%, amr); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Ala3685= (c.11055C>T)?

DNAH1 p.Ala3685= (c.11055C>T) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Ala3685= (c.11055C>T) in the general population?

DNAH1 p.Ala3685= (c.11055C>T) is rare (popmax 0.408%, amr) (gnomAD).

DNAH1 p.Ala3685=

c.11055C>T · rs180952807 · VCV478394

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.408%, amr)

Conditions

spermatogenic failure 18

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 -14	GERP -3.8
Overall
CADD	0.336	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.408% Admixed American · 245/60,010 alleles

Filtering AF 0.366% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.35%

Overall 0.0166% 268/1,613,886 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.408%	245
Middle Eastern	0.033%	3,031
East Asian	0.0178%	5,610
African / African-American	0.00666%	15,012
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Finnishnot grpmax-eligible	0.00156%	63,918
European (non-Finnish)	0.000339%	294,969

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: DNAH1
Protein: p.Ala3685=
Coding: c.11055C>T
MANE Select: NM_015512
dbSNP: rs180952807
Type: single nucleotide variant
Location: chr3:52395394 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 3685: a UniProt-annotated variant site (in spgf18); the 'aaa 6' region

Full DNAH1 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

Also linked: ciliary dyskinesia, primary, 37

Similar variants

DNAH1 c.1034-2A>G Likely pathogenic ★★ same condition
DNAH1 c.10474+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAH1 c.10968+2C>T Likely pathogenic ★★ same condition
DNAH1 c.5244+1G>A Likely pathogenic ★★ same condition
DNAH1 p.Arg1702Ter Pathogenic ★★ same condition
DNAH1 p.Arg2479Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH1 p.Arg2622Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH1 p.Arg2724Ter Pathogenic ★★ same condition

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/dnah1-p-ala3685 (accessed [today's date]).

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