Is DNAH1 p.Asp662= (c.1986C>T) pathogenic?

DNAH1 p.Asp662= (c.1986C>T) is classified Benign/Likely benign in DNAH1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). Low-frequency (popmax 1.35%, sas); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Asp662= (c.1986C>T)?

DNAH1 p.Asp662= (c.1986C>T) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Asp662= (c.1986C>T) in the general population?

DNAH1 p.Asp662= (c.1986C>T) is low-frequency (popmax 1.35%, sas) (gnomAD).

DNAH1 p.Asp662=

c.1986C>T · rs376991251 · VCV478422

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.35%, 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 1.7	GERP 1.8, phastCons 1
Overall
CADD	9.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.35% South Asian · 1,199/88,780 alleles

Filtering AF 1.29% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.26%

Overall 0.15% 2,398/1,600,494 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.35%	74
Middle Eastern	0.48%	208
Remaining individualsnot grpmax-eligible	0.192%	520
European (non-Finnish)	0.0848%	1,179
Admixed American	0.0464%	2,155
Finnishnot grpmax-eligible	0.0379%	2,639
African / African-American	0.00535%	18,696
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,238

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.Asp662=
Coding: c.1986C>T
MANE Select: NM_015512
dbSNP: rs376991251
Type: single nucleotide variant
Location: chr3:52347854 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 662: 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.Asp662Asn Uncertain significance ★ ⚠ 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-asp662 (accessed [today's date]).

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