Is DNAH1 p.Ser2001Phe (c.6002C>T) pathogenic?

DNAH1 p.Ser2001Phe (c.6002C>T) is classified Uncertain significance in DNAH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-03-21). AlphaMissense: likely pathogenic (0.987); Very rare (popmax 0.00223%, eas); Associated with spermatogenic failure 18.

What condition is associated with DNAH1 p.Ser2001Phe (c.6002C>T)?

DNAH1 p.Ser2001Phe (c.6002C>T) is associated with spermatogenic failure 18, ciliary dyskinesia, primary, 37 (ClinVar).

How common is DNAH1 p.Ser2001Phe (c.6002C>T) in the general population?

DNAH1 p.Ser2001Phe (c.6002C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DNAH1 p.Ser2001Phe (c.6002C>T)?

AlphaMissense predicts likely pathogenic (score 0.987) — an in-silico prediction, not a clinical call.

DNAH1 p.Ser2001Phe

c.6002C>T · rs772200369 · VCV478472

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.987 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

spermatogenic failure 18

Computational evidence

Protein change
AlphaMissense	0.987	likely pathogenic · top 3% in DNAH1
REVEL	0.849	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 0.94, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 42 kb · p 1.9e-16 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,892 alleles

Overall 0.000186% 3/1,613,740 alleles · very rare exomes 2/1,461,498 · genomes 1/152,242 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,892
Admixed American	0.00167%	60,014
European (non-Finnish)	8.48e-05%	1,179,796

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.Ser2001Phe
Coding: c.6002C>T
MANE Select: NM_015512
dbSNP: rs772200369
Type: single nucleotide variant
Location: chr3:52369883 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 2001: a UniProt-annotated variant site (in spgf18); the 'aaa 2' 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-ser2001phe (accessed [today's date]).

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