Is MYO7B p.Arg625Trp (c.1873C>T) pathogenic?

MYO7B p.Arg625Trp (c.1873C>T) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-16). AlphaMissense: likely benign (0.0839); Ultra-rare (popmax 0.0287%, sas).

How common is MYO7B p.Arg625Trp (c.1873C>T) in the general population?

MYO7B p.Arg625Trp (c.1873C>T) is ultra-rare (popmax 0.0287%, sas) (gnomAD).

What do computational predictors say about MYO7B p.Arg625Trp (c.1873C>T)?

AlphaMissense predicts likely benign (score 0.0839) — an in-silico prediction, not a clinical call.

MYO7B p.Arg625Trp

c.1873C>T · rs763019482 · VCV2377613

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0839 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0287%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0839	likely benign
REVEL	0.528	indeterminate
SaProt	LLR -13.93	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.94	GERP 1.9, phastCons 0.4
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	24.3	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 0.0287% South Asian · 25/86,998 alleles

Filtering AF 0.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.017%

Overall 0.00415% 66/1,589,370 alleles · ultra-rare exomes 60/1,437,202 · genomes 6/152,168 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0287%	3,480
Remaining individualsnot grpmax-eligible	0.0081%	12,350
East Asian	0.00681%	14,682
African / African-American	0.00403%	24,791
Admixed American	0.00356%	28,076
European (non-Finnish)	0.0024%	41,727

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.Arg625Trp
Coding: c.1873C>T
MANE Select: NM_001393586
dbSNP: rs763019482
Type: single nucleotide variant
Location: chr2:127590110 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 625: the myosin motor domain

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

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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/myo7b-p-arg625trp (accessed [today's date]).

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