Is MYO7B p.Arg873Cys (c.2617C>T) pathogenic?

MYO7B p.Arg873Cys (c.2617C>T) is classified Uncertain significance in MYO7B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). AlphaMissense: likely benign (0.1538); Ultra-rare (popmax 0.0167%, mid).

How common is MYO7B p.Arg873Cys (c.2617C>T) in the general population?

MYO7B p.Arg873Cys (c.2617C>T) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about MYO7B p.Arg873Cys (c.2617C>T)?

AlphaMissense predicts likely benign (score 0.1538) — an in-silico prediction, not a clinical call.

MYO7B p.Arg873Cys

c.2617C>T · rs1411735494 · VCV2588521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1538 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1538	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -10.60	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.13	GERP -1.8
Regional constraint	o/e 0.94	unconstrained · MANE · 69 kb · p 0.0075 · regional, not allelic
Overall
CADD	17.22	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 0.0167% Middle Eastern · 1/5,986 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00119%

Overall 0.00226% 35/1,551,030 alleles · ultra-rare exomes 30/1,398,822 · genomes 5/152,208 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,986
Remaining individualsnot grpmax-eligible	0.00499%	20,028
South Asian	0.00476%	21,011
Admixed American	0.00392%	25,492
European (non-Finnish)	0.00209%	47,785
African / African-American	0.00137%	73,042

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.Arg873Cys
Coding: c.2617C>T
MANE Select: NM_001393586
dbSNP: rs1411735494
Type: single nucleotide variant
Location: chr2:127607398 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 873: the iq 6 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-arg873cys (accessed [today's date]).

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