Is DNAH1 p.Ala162Val (c.485C>T) pathogenic?

DNAH1 p.Ala162Val (c.485C>T) is classified Uncertain significance in DNAH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-07). AlphaMissense: likely benign (0.0845); Very rare (popmax 0.0055%, sas); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Ala162Val (c.485C>T)?

DNAH1 p.Ala162Val (c.485C>T) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Ala162Val (c.485C>T) in the general population?

DNAH1 p.Ala162Val (c.485C>T) is very rare (popmax 0.0055%, sas) (gnomAD).

What do computational predictors say about DNAH1 p.Ala162Val (c.485C>T)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

DNAH1 p.Ala162Val

c.485C>T · rs993782683 · VCV958350

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0055%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

spermatogenic failure 18

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.115	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 1.7	GERP 3.7, phastCons 0.003
Regional constraint	o/e 1.04	unconstrained · MANE · 30 kb · p 0.21 · regional, not allelic
Overall
CADD	12.04	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 0.0055% South Asian · 5/90,904 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00136% 22/1,613,054 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0055%	18,181
Finnishnot grpmax-eligible	0.00314%	31,882
Remaining individualsnot grpmax-eligible	0.0016%	62,430
European (non-Finnish)	0.00119%	84,261

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.Ala162Val
Coding: c.485C>T
MANE Select: NM_015512
dbSNP: rs993782683
Type: single nucleotide variant
Location: chr3:52326218 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 162: 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 p.Ala162Asp Uncertain significance ★ ⚠ same residue
DNAH1 p.Ala162Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ala162val (accessed [today's date]).

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