Is DNAH7 p.Ser3657Arg (c.10971C>A) pathogenic?

DNAH7 p.Ser3657Arg (c.10971C>A) is classified Uncertain significance in DNAH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-04). AlphaMissense: likely pathogenic (0.844); Absent from gnomAD v4.1; Associated with ciliary dyskinesia, primary, 50.

What condition is associated with DNAH7 p.Ser3657Arg (c.10971C>A)?

DNAH7 p.Ser3657Arg (c.10971C>A) is associated with ciliary dyskinesia, primary, 50 (ClinVar).

How common is DNAH7 p.Ser3657Arg (c.10971C>A) in the general population?

DNAH7 p.Ser3657Arg (c.10971C>A) is absent from gnomAD v4.1 (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DNAH7 p.Ser3657Arg (c.10971C>A)?

AlphaMissense predicts likely pathogenic (score 0.844) — an in-silico prediction, not a clinical call.

DNAH7 p.Ser3657Arg

c.10971C>A · rs2469221804 · VCV3067995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.844 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

ciliary dyskinesia, primary, 50

Computational evidence

Protein change
AlphaMissense	0.844	likely pathogenic
REVEL	0.233	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 1.2	GERP 1.5, phastCons 0.99
Regional constraint	o/e 1.02	unconstrained · MANE · 331 kb · p 0.14 · regional, not allelic
Overall
CADD	21.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAH7
Protein: p.Ser3657Arg
Coding: c.10971C>A
MANE Select: NM_018897
dbSNP: rs2469221804
Type: single nucleotide variant
Location: chr2:195777893 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)

Full DNAH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ciliary dyskinesia, primary, 50 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAH7 p.Ser3657Cys Uncertain significance ★ ⚠ same residue
DNAH7 p.Ser3657Gly Uncertain significance ★ ⚠ same residue
DNAH7 p.Asn2116Ser Uncertain significance ★★ ⚠ same condition
DNAH7 c.11869-2A>C Likely pathogenic ★ same condition
DNAH7 c.4647+1G>A Pathogenic ★ same condition
DNAH7 c.870-1G>T Likely pathogenic ★ same condition
DNAH7 p.Arg1437Ter Likely pathogenic ★ same condition
DNAH7 p.Arg2889Ter 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/dnah7-p-ser3657arg (accessed [today's date]).

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