Is DNAH1 p.Val2846= (c.8538A>G) pathogenic?

DNAH1 p.Val2846= (c.8538A>G) is classified Benign/Likely benign in DNAH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). Rare (popmax 0.187%, sas); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Val2846= (c.8538A>G)?

DNAH1 p.Val2846= (c.8538A>G) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Val2846= (c.8538A>G) in the general population?

DNAH1 p.Val2846= (c.8538A>G) is rare (popmax 0.187%, sas) (gnomAD).

DNAH1 p.Val2846=

c.8538A>G · rs538052520 · VCV757303

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.187%, sas)

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 0.67	GERP -0.63, phastCons 1
Overall
CADD	2.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.187% South Asian · 157/84,084 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.154%

Overall 0.0113% 175/1,552,556 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.187%	536
Middle Eastern	0.0334%	2,995
Remaining individualsnot grpmax-eligible	0.0183%	5,475
East Asian	0.00244%	40,960
European (non-Finnish)	0.000349%	286,863

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.Val2846=
Coding: c.8538A>G
MANE Select: NM_015512
dbSNP: rs538052520
Type: single nucleotide variant
Location: chr3:52385360 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 2846: a UniProt-annotated variant site (in spgf18); an α-helix; the 'stalk' 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-val2846 (accessed [today's date]).

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