Is DNAH1 p.Arg1663Cys (c.4987C>T) pathogenic?

DNAH1 p.Arg1663Cys (c.4987C>T) is classified Benign in DNAH1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1182); Low-frequency (popmax 3.32%, amr); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Arg1663Cys (c.4987C>T)?

DNAH1 p.Arg1663Cys (c.4987C>T) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Arg1663Cys (c.4987C>T) in the general population?

DNAH1 p.Arg1663Cys (c.4987C>T) is low-frequency (popmax 3.32%, amr) (gnomAD).

What do computational predictors say about DNAH1 p.Arg1663Cys (c.4987C>T)?

AlphaMissense predicts likely benign (score 0.1182) — an in-silico prediction, not a clinical call.

DNAH1 p.Arg1663Cys

c.4987C>T · rs17052097 · VCV478453

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1182 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.32%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

spermatogenic failure 18

Computational evidence

Protein change
AlphaMissense	0.1182	likely benign
REVEL	0.198	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.94, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 42 kb · p 1.9e-16 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.32% Admixed American · 1,990/59,926 alleles

Filtering AF 3.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.15%

Overall 0.219% 3,526/1,613,448 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	3.32%	30
East Asian	2.2%	45
Remaining individualsnot grpmax-eligible	0.179%	558
African / African-American	0.0973%	1,028
Middle Eastern	0.0497%	2,011
South Asian	0.0484%	2,067
Ashkenazi Jewishnot grpmax-eligible	0.0406%	2,466
Finnishnot grpmax-eligible	0.025%	3,997
European (non-Finnish)	0.0244%	4,096

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.Arg1663Cys
Coding: c.4987C>T
MANE Select: NM_015512
dbSNP: rs17052097
Type: single nucleotide variant
Location: chr3:52362394 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 1663: a UniProt-annotated variant site (in spgf18); the 'aaa 1' region; a UniProt-annotated variant site (in)

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.Arg1663Gly 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-arg1663cys (accessed [today's date]).

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