Is MYO7A p.Arg702Cys (c.2104C>T) pathogenic?

MYO7A p.Arg702Cys (c.2104C>T) is classified Uncertain significance in MYO7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely benign (0.1946); Very rare (popmax 0.00533%, afr).

How common is MYO7A p.Arg702Cys (c.2104C>T) in the general population?

MYO7A p.Arg702Cys (c.2104C>T) is very rare (popmax 0.00533%, afr) (gnomAD).

What do computational predictors say about MYO7A p.Arg702Cys (c.2104C>T)?

AlphaMissense predicts likely benign (score 0.1946) — an in-silico prediction, not a clinical call.

MYO7A p.Arg702Cys

c.2104C>T · rs377529562 · VCV1412877

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1946 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00533%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1946	likely benign
REVEL	0.538	indeterminate
SaProt	LLR -12.81	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 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 84 kb · p 0.0065 · regional, not allelic
Overall
CADD	23.4	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 0.00533% African / African-American · 4/75,044 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00143% 23/1,613,190 alleles · very rare exomes 18/1,460,890 · genomes 5/152,300 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,761
East Asian	0.00223%	44,874
Admixed American	0.00167%	60,026
Finnishnot grpmax-eligible	0.00158%	63,270
European (non-Finnish)	0.00127%	78,657
South Asian	0.0011%	91,068

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: MYO7A
Protein: p.Arg702Cys
Coding: c.2104C>T
MANE Select: NM_000260
dbSNP: rs377529562
Type: single nucleotide variant
Location: chr11:77175381 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 702: the myosin motor domain

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MYO7A p.Arg702His Uncertain significance ★★ ⚠ same residue
MYO7A p.Arg702= Conflicting classifications of pathogenicity ★ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same type
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same type
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same type
MYO7A p.Arg668Cys Pathogenic ★★★ same type
MYO7A p.Arg853His Likely pathogenic ★★★ 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/myo7a-p-arg702cys (accessed [today's date]).

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