Is DNAH1 p.Ile3208= (c.9624C>T) pathogenic?

DNAH1 p.Ile3208= (c.9624C>T) is classified Benign in DNAH1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Common (popmax 19.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Ile3208= (c.9624C>T)?

DNAH1 p.Ile3208= (c.9624C>T) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

DNAH1 p.Ile3208=

Q: How common is DNAH1 p.Ile3208= (c.9624C>T) in the general population?

DNAH1 p.Ile3208= (c.9624C>T) is common (popmax 19.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9624C>T · rs61734628 · VCV478514

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 19.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

spermatogenic failure 18

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.232	benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.63 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.1	GERP -3.8
Overall
CADD	0.251	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.5% African / African-American · 14,252/73,110 alleles

Filtering AF 19.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.1%

Overall 1.39% 21,605/1,551,744 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19.5%	5
Remaining individualsnot grpmax-eligible	1.66%	60
South Asian	1.52%	66
Admixed American	1.41%	71
Middle Eastern	1.06%	94
European (non-Finnish)	0.373%	268
Finnishnot grpmax-eligible	0.0333%	3,002
East Asian	0.0122%	8,181

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.Ile3208=
Coding: c.9624C>T
MANE Select: NM_015512
dbSNP: rs61734628
Type: single nucleotide variant
Location: chr3:52390937 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 3208: a UniProt-annotated variant site (in spgf18); the 'aaa 5' 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.Ile3208fs Pathogenic ★ 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-ile3208 (accessed [today's date]).

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