Is DNAH1 p.Pro462= (c.1386C>T) pathogenic?

DNAH1 p.Pro462= (c.1386C>T) is classified Likely benign in DNAH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). Very rare (popmax 0.00678%, nfe); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Pro462= (c.1386C>T)?

DNAH1 p.Pro462= (c.1386C>T) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Pro462= (c.1386C>T) in the general population?

DNAH1 p.Pro462= (c.1386C>T) is very rare (popmax 0.00678%, nfe) (gnomAD).

DNAH1 p.Pro462=

c.1386C>T · rs750795432 · VCV1123946

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00678%, nfe)

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
Overall
CADD	0.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00678% European (non-Finnish) · 80/1,179,872 alleles

Filtering AF 0.00555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00527% 85/1,613,854 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00678%	14,748
Remaining individualsnot grpmax-eligible	0.0032%	31,231
African / African-American	0.00267%	37,470
South Asian	0.0011%	91,082

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.Pro462=
Coding: c.1386C>T
MANE Select: NM_015512
dbSNP: rs750795432
Type: single nucleotide variant
Location: chr3:52344589 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 462: 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.Pro462Ser Benign/Likely benign ★★ 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
DNAH1 p.Arg2622Ter 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-pro462 (accessed [today's date]).

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