Is DNAH1 p.Pro43= (c.129A>G) pathogenic?

DNAH1 p.Pro43= (c.129A>G) is classified Likely benign in DNAH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-15). Very rare (popmax 0.00534%, afr); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Pro43= (c.129A>G)?

DNAH1 p.Pro43= (c.129A>G) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Pro43= (c.129A>G) in the general population?

DNAH1 p.Pro43= (c.129A>G) is very rare (popmax 0.00534%, afr) (gnomAD).

DNAH1 p.Pro43=

c.129A>G · rs373701749 · VCV1573904

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

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 1.5	GERP 1.1, phastCons 0.064
Overall
CADD	3.726	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,900 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000372% 6/1,613,772 alleles · very rare exomes 2/1,461,644 · genomes 4/152,128 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,725
Admixed American	0.00333%	29,997

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.Pro43=
Coding: c.129A>G
MANE Select: NM_015512
dbSNP: rs373701749
Type: single nucleotide variant
Location: chr3:52322571 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 43: the 'stem' region; the 'disordered' 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-pro43 (accessed [today's date]).

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