Is DNAH7 p.Arg3548Trp (c.10642C>T) pathogenic?

DNAH7 p.Arg3548Trp (c.10642C>T) is classified Uncertain significance in DNAH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-20). AlphaMissense: likely pathogenic (0.89); Ultra-rare (popmax 0.0164%, mid).

How common is DNAH7 p.Arg3548Trp (c.10642C>T) in the general population?

DNAH7 p.Arg3548Trp (c.10642C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DNAH7 p.Arg3548Trp (c.10642C>T)?

AlphaMissense predicts likely pathogenic (score 0.89) — an in-silico prediction, not a clinical call.

DNAH7 p.Arg3548Trp

c.10642C>T · VCV4013237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.89 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
AlphaMissense	0.89	likely pathogenic
REVEL	0.513	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 331 kb · p 0.14 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00161% 26/1,614,016 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00878%	11,386
African / African-American	0.00534%	18,728
East Asian	0.00223%	44,886
Admixed American	0.00167%	60,002
European (non-Finnish)	0.000932%	107,274

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: DNAH7
Protein: p.Arg3548Trp
Coding: c.10642C>T
MANE Select: NM_018897
Type: single nucleotide variant
Location: chr2:195794412 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Residue 3548: the 'aaa 6' region

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

Similar variants

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DNAH7 p.Asp1219Gly Uncertain significance ★★ ⚠ same type
DNAH7 p.Asp1787Gly Uncertain significance ★★ same type
DNAH7 p.Asp2867Tyr Uncertain significance ★★ ⚠ same type
DNAH7 p.Ile1203Met Uncertain significance ★★ ⚠ same type
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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-arg3548trp (accessed [today's date]).

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