Is DNAH1 p.Phe3590= (c.10770C>T) pathogenic?

DNAH1 p.Phe3590= (c.10770C>T) is classified Benign/Likely benign in DNAH1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-08). Rare (popmax 0.179%, eas); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Phe3590= (c.10770C>T)?

DNAH1 p.Phe3590= (c.10770C>T) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Phe3590= (c.10770C>T) in the general population?

DNAH1 p.Phe3590= (c.10770C>T) is rare (popmax 0.179%, eas) (gnomAD).

DNAH1 p.Phe3590=

c.10770C>T · rs369033532 · VCV733590

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.179%, eas)

Conditions

spermatogenic failure 18

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.3	GERP -3.2
Overall
CADD	2.452	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.179% East Asian · 80/44,732 alleles

Filtering AF 0.147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.00624% 100/1,602,252 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.179%	559
African / African-American	0.004%	24,971
Remaining individualsnot grpmax-eligible	0.00323%	30,992
European (non-Finnish)	0.00128%	78,157

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.Phe3590=
Coding: c.10770C>T
MANE Select: NM_015512
dbSNP: rs369033532
Type: single nucleotide variant
Location: chr3:52394608 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 3590: a UniProt-annotated variant site (in spgf18)

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-phe3590 (accessed [today's date]).

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