Is MYO7B p.Arg1664Cys (c.4990C>T) pathogenic?

MYO7B p.Arg1664Cys (c.4990C>T) is classified Benign in MYO7B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-21). AlphaMissense: likely benign (0.12); Rare (popmax 0.601%, amr); Associated with MYO7B-related disorder.

What condition is associated with MYO7B p.Arg1664Cys (c.4990C>T)?

MYO7B p.Arg1664Cys (c.4990C>T) is associated with MYO7B-related disorder (ClinVar).

How common is MYO7B p.Arg1664Cys (c.4990C>T) in the general population?

MYO7B p.Arg1664Cys (c.4990C>T) is rare (popmax 0.601%, amr) (gnomAD).

What do computational predictors say about MYO7B p.Arg1664Cys (c.4990C>T)?

AlphaMissense predicts likely benign (score 0.12) — an in-silico prediction, not a clinical call.

MYO7B p.Arg1664Cys

c.4990C>T · rs200195243 · VCV3039833

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.12 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.601%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYO7B-related disorder

Computational evidence

Protein change
AlphaMissense	0.12	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -10.04	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 0.62	GERP -0.76
Regional constraint	o/e 1.07	unconstrained · MANE · 7,741 bp · p 0.063 · regional, not allelic
Overall
CADD	22.2	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 R1638C vs ClinVar R1664C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.601% Admixed American · 360/59,904 alleles

Filtering AF 0.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.53%

Overall 0.0254% 409/1,611,168 alleles · rare exomes 368/1,458,818 · genomes 41/152,350 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.601%	166
Remaining individualsnot grpmax-eligible	0.0208%	4,799
African / African-American	0.0187%	5,359
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,546
South Asian	0.0022%	45,479
European (non-Finnish)	0.00161%	62,040

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.Arg1664Cys
Coding: c.4990C>T
MANE Select: NM_001393586
dbSNP: rs200195243
Type: single nucleotide variant
Location: chr2:127631258 (GRCh38)
Gene constraint: LOEUF 0.956 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.34 · 3 PDB
Residue 1638 UniProt numbering: 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-arg1664cys (accessed [today's date]).

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