Is MYO7B p.Arg1947Cys (c.5839C>T) pathogenic?

MYO7B p.Arg1947Cys (c.5839C>T) is classified Benign in MYO7B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-19). AlphaMissense: likely benign (0.2238); Low-frequency (popmax 2.68%, sas); Associated with MYO7B-related disorder.

What condition is associated with MYO7B p.Arg1947Cys (c.5839C>T)?

MYO7B p.Arg1947Cys (c.5839C>T) is associated with MYO7B-related disorder (ClinVar).

How common is MYO7B p.Arg1947Cys (c.5839C>T) in the general population?

MYO7B p.Arg1947Cys (c.5839C>T) is low-frequency (popmax 2.68%, sas) (gnomAD).

What do computational predictors say about MYO7B p.Arg1947Cys (c.5839C>T)?

AlphaMissense predicts likely benign (score 0.2238) — an in-silico prediction, not a clinical call.

MYO7B p.Arg1947Cys

c.5839C>T · rs376214274 · VCV3042741

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2238 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.68%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYO7B-related disorder

Computational evidence

Protein change
AlphaMissense	0.2238	likely benign
REVEL	0.723	pathogenic-leaning
SaProt	LLR -10.20	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 7,741 bp · p 0.063 · regional, not allelic
Overall
CADD	33.0	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 R1921C vs ClinVar R1947C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.68% South Asian · 2,381/88,896 alleles

Filtering AF 2.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.55%

Overall 0.16% 2,559/1,603,542 alleles · low-frequency exomes 2,417/1,451,212 · genomes 142/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.68%	37
Middle Eastern	0.165%	605
Remaining individualsnot grpmax-eligible	0.129%	777
African / African-American	0.0147%	6,801
European (non-Finnish)	0.00647%	15,465
Admixed American	0.0017%	58,850

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.Arg1947Cys
Coding: c.5839C>T
MANE Select: NM_001393586
dbSNP: rs376214274
Type: single nucleotide variant
Location: chr2:127635740 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1921 UniProt numbering: the ferm 2 domain; the 'mediates interaction with cdhr2, cdhr5 and ush1c' region

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

Disease context

MYO7B-related disorder

Similar variants

MYO7B p.Ala397Ser Uncertain significance ⚠ same condition
MYO7B c.1081-10G>T Benign same condition
MYO7B c.1691-7T>C Benign same condition
MYO7B c.2339+4C>T Benign same condition
MYO7B c.4333+8C>A Likely benign same condition
MYO7B c.5714-7C>T Benign same condition
MYO7B c.5821-8T>C Benign same condition
MYO7B c.6123+9T>C Benign same condition

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-arg1947cys (accessed [today's date]).

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