Is DNAH7 p.Arg3407Cys (c.10219C>T) pathogenic?

DNAH7 p.Arg3407Cys (c.10219C>T) is classified Uncertain significance in DNAH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: likely benign (0.1694); Ultra-rare (popmax 0.0349%, afr).

How common is DNAH7 p.Arg3407Cys (c.10219C>T) in the general population?

DNAH7 p.Arg3407Cys (c.10219C>T) is ultra-rare (popmax 0.0349%, afr) (gnomAD).

What do computational predictors say about DNAH7 p.Arg3407Cys (c.10219C>T)?

AlphaMissense predicts likely benign (score 0.1694) — an in-silico prediction, not a clinical call.

DNAH7 p.Arg3407Cys

c.10219C>T · rs202016271 · VCV3084076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1694 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0349%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1694	likely benign
REVEL	0.182	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.18, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 331 kb · p 0.14 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0349% African / African-American · 26/74,506 alleles

Filtering AF 0.0244% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00324% 52/1,605,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0349%	2,866
Middle Eastern	0.0165%	6,058
Admixed American	0.00852%	11,731
Remaining individualsnot grpmax-eligible	0.00644%	15,533
East Asian	0.00225%	44,522
South Asian	0.00224%	44,550
European (non-Finnish)	0.0011%	90,512

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.Arg3407Cys
Coding: c.10219C>T
MANE Select: NM_018897
dbSNP: rs202016271
Type: single nucleotide variant
Location: chr2:195799430 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Residue 3407: the 'aaa 6' region

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

Similar variants

DNAH7 p.Arg3407His 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-arg3407cys (accessed [today's date]).

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