Is DNAH7 p.Arg756Cys (c.2266C>T) pathogenic?

DNAH7 p.Arg756Cys (c.2266C>T) is classified Uncertain significance in DNAH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.2516); Very rare (popmax 0.0044%, sas).

How common is DNAH7 p.Arg756Cys (c.2266C>T) in the general population?

DNAH7 p.Arg756Cys (c.2266C>T) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about DNAH7 p.Arg756Cys (c.2266C>T)?

AlphaMissense predicts likely benign (score 0.2516) — an in-silico prediction, not a clinical call.

DNAH7 p.Arg756Cys

c.2266C>T · VCV4242709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2516 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Computational evidence

Protein change
AlphaMissense	0.2516	likely benign
REVEL	0.47	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 331 kb · p 0.14 · regional, not allelic
Overall
CADD	25.5	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 0.0044% South Asian · 4/90,982 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000992% 16/1,613,626 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,746
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000932%	107,260

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.Arg756Cys
Coding: c.2266C>T
MANE Select: NM_018897
Type: single nucleotide variant
Location: chr2:195960885 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Residue 756: the 'stem' region

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

Similar variants

DNAH7 p.Arg756His Uncertain significance ★ same residue
DNAH7 p.Arg1884Gln Uncertain significance ★★ ⚠ same type
DNAH7 p.Arg3272Gln Uncertain significance ★★ ⚠ same type
DNAH7 p.Asn2116Ser Uncertain significance ★★ ⚠ same type
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

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-arg756cys (accessed [today's date]).

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