Is DNAH7 p.Arg3295Pro (c.9884G>C) pathogenic?

DNAH7 p.Arg3295Pro (c.9884G>C) is classified Uncertain significance in DNAH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). AlphaMissense: ambiguous (0.4664); Very rare (popmax 0.000344%, nfe).

How common is DNAH7 p.Arg3295Pro (c.9884G>C) in the general population?

DNAH7 p.Arg3295Pro (c.9884G>C) is very rare (popmax 0.000344%, nfe) (gnomAD).

What do computational predictors say about DNAH7 p.Arg3295Pro (c.9884G>C)?

AlphaMissense predicts ambiguous (score 0.4664) — an in-silico prediction, not a clinical call.

DNAH7 p.Arg3295Pro

c.9884G>C · VCV3503685

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4664 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000344%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4664	ambiguous
REVEL	0.127	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.3	GERP -3.9
Regional constraint	o/e 1.02	unconstrained · MANE · 331 kb · p 0.14 · regional, not allelic
Overall
CADD	0.184	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 0.000344% European (non-Finnish) · 4/1,163,976 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00028% 4/1,427,596 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: DNAH7
Protein: p.Arg3295Pro
Coding: c.9884G>C
MANE Select: NM_018897
Type: single nucleotide variant
Location: chr2:195809749 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)

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

Similar variants

DNAH7 p.Arg3295Gln Likely benign ★ 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-arg3295pro (accessed [today's date]).

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