Is DNAH1 p.Ser1802Pro (c.5404T>C) pathogenic?

DNAH1 p.Ser1802Pro (c.5404T>C) is classified Uncertain significance in DNAH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-02). AlphaMissense: likely pathogenic (0.9059); Very rare (popmax 6.84e-05%).

How common is DNAH1 p.Ser1802Pro (c.5404T>C) in the general population?

DNAH1 p.Ser1802Pro (c.5404T>C) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about DNAH1 p.Ser1802Pro (c.5404T>C)?

AlphaMissense predicts likely pathogenic (score 0.9059) — an in-silico prediction, not a clinical call.

DNAH1 p.Ser1802Pro

c.5404T>C · VCV4660693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9059 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.9059	likely pathogenic
REVEL	0.205	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.46	GERP -0.66, phastCons 0.002
Regional constraint	o/e 0.86	unconstrained · MANE · 42 kb · p 1.9e-16 · regional, not allelic
Overall
CADD	19.98	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 6.84e-05%

Overall 6.84e-05% 1/1,461,694 alleles · very rare

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.Ser1802Pro
Coding: c.5404T>C
MANE Select: NM_015512
Type: single nucleotide variant
Location: chr3:52364905 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Residue 1802: a UniProt-annotated variant site (in spgf18)

Full DNAH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH1 p.Ser1802= Likely benign ★ same residue
BAP1 p.Gln410Ter Pathogenic ★★ same type
DNAH1 c.1034-2A>G Likely pathogenic ★★ same type
DNAH1 c.10474+1G>A Pathogenic/Likely pathogenic ★★ same type
DNAH1 c.10968+2C>T Likely pathogenic ★★ same type
DNAH1 c.2526+1G>A Likely pathogenic ★★ same type
DNAH1 c.5244+1G>A Likely pathogenic ★★ same type
DNAH1 p.Arg1702Ter Pathogenic ★★ same type

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-ser1802pro (accessed [today's date]).

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