Is DNAH1 p.Asp830Ala (c.2489A>C) pathogenic?

DNAH1 p.Asp830Ala (c.2489A>C) is classified Uncertain significance in DNAH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-07). AlphaMissense: likely benign (0.2046); Ultra-rare (popmax 0.0734%, afr); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Asp830Ala (c.2489A>C)?

DNAH1 p.Asp830Ala (c.2489A>C) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Asp830Ala (c.2489A>C) in the general population?

DNAH1 p.Asp830Ala (c.2489A>C) is ultra-rare (popmax 0.0734%, afr) (gnomAD).

What do computational predictors say about DNAH1 p.Asp830Ala (c.2489A>C)?

AlphaMissense predicts likely benign (score 0.2046) — an in-silico prediction, not a clinical call.

DNAH1 p.Asp830Ala

c.2489A>C · rs376327672 · VCV582738

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2046 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0734%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

spermatogenic failure 18

Computational evidence

Protein change
AlphaMissense	0.2046	likely benign
REVEL	0.114	moderately 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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 30 kb · p 0.21 · regional, not allelic
Overall
CADD	24.1	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0734% African / African-American · 55/74,942 alleles

Filtering AF 0.0578% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0523%

Overall 0.00403% 65/1,613,858 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0734%	1,363
Remaining individualsnot grpmax-eligible	0.00961%	10,411
Admixed American	0.00666%	15,004

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.Asp830Ala
Coding: c.2489A>C
MANE Select: NM_015512
dbSNP: rs376327672
Type: single nucleotide variant
Location: chr3:52349383 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 830: the 'stem' 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-asp830ala (accessed [today's date]).

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