Is MYO7B p.Arg1129Trp (c.3385C>T) pathogenic?

MYO7B p.Arg1129Trp (c.3385C>T) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-19). AlphaMissense: likely benign (0.1332); Rare (popmax 0.656%, afr).

How common is MYO7B p.Arg1129Trp (c.3385C>T) in the general population?

MYO7B p.Arg1129Trp (c.3385C>T) is rare (popmax 0.656%, afr) (gnomAD).

What do computational predictors say about MYO7B p.Arg1129Trp (c.3385C>T)?

AlphaMissense predicts likely benign (score 0.1332) — an in-silico prediction, not a clinical call.

MYO7B p.Arg1129Trp

c.3385C>T · rs61742351 · VCV3040129

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1332 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.656%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1332	likely benign
REVEL	0.502	indeterminate
SaProt	LLR -11.58	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP 0.41, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1103W vs ClinVar R1129W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.656% African / African-American · 491/74,902 alleles

Filtering AF 0.608% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.589%

Overall 0.0411% 661/1,609,700 alleles · rare exomes 344/1,457,338 · genomes 317/152,362 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.656%	153
Admixed American	0.0854%	1,171
Remaining individualsnot grpmax-eligible	0.0545%	1,834
Middle Eastern	0.0174%	5,738
European (non-Finnish)	0.00687%	14,548
East Asian	0.00448%	22,338
Finnishnot grpmax-eligible	0.00157%	63,564

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: MYO7B
Protein: p.Arg1129Trp
Coding: c.3385C>T
MANE Select: NM_001393586
dbSNP: rs61742351
Type: single nucleotide variant
Location: chr2:127612590 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1103 UniProt numbering: the 'mediates interaction with anks4b' region; the myth4 1 domain

Full MYO7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MYO7B p.Thr349Met Uncertain significance ★★ ⚠ same type
MYO7B p.Ile1309Val Benign ★★ same type
MYO7B p.Val1556Ile Benign ★★ same type
MYO7B p.Val1876= Benign ★★ same type
MYO7B p.Ala1010Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1092Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1109Thr Uncertain significance ★ ⚠ same type
MYO7B p.Ala1126Thr 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/myo7b-p-arg1129trp (accessed [today's date]).

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