Is MYH3 p.Arg1663Gly (c.4987C>G) pathogenic?

MYH3 p.Arg1663Gly (c.4987C>G) is classified Uncertain significance in MYH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). AlphaMissense: likely benign (0.3327); Very rare (popmax 0.00133%, afr).

How common is MYH3 p.Arg1663Gly (c.4987C>G) in the general population?

MYH3 p.Arg1663Gly (c.4987C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about MYH3 p.Arg1663Gly (c.4987C>G)?

AlphaMissense predicts likely benign (score 0.3327) — an in-silico prediction, not a clinical call.

MYH3 p.Arg1663Gly

c.4987C>G · rs777159320 · VCV1370997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3327 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3327	likely benign
REVEL	0.763	pathogenic-leaning
SaProt	LLR -13.71	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 11 kb · p 1.7e-05 · regional, not allelic
Overall
CADD	27.3	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 0.00133% African / African-American · 1/75,038 alleles

Overall 6.2e-05% 1/1,613,766 alleles · very rare exomes 1/1,461,434 · genomes 0/152,332 · joint denominator

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: MYH3
Protein: p.Arg1663Gly
Coding: c.4987C>G
MANE Select: NM_002470
dbSNP: rs777159320
Type: single nucleotide variant
Location: chr17:10631986 (GRCh38)
Gene constraint: LOEUF 0.604 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.35
Residue 1663: a UniProt-annotated variant site (in cpsfs1b)

Full MYH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MYH3 p.Arg1663Gln Uncertain significance ★ ⚠ same residue
MYH3 p.Arg1663Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
MYH3 p.Arg1663= Likely benign ★ same residue
MYH3 c.1581+1G>A Pathogenic/Likely pathogenic ★★ same type
MYH3 c.2682+1G>A Likely pathogenic ★★ same type
MYH3 c.533+1G>A Likely pathogenic ★★ same type
MYH3 c.5563-1G>C Likely pathogenic ★★ same type
MYH3 c.-9+1G>A Pathogenic/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/myh3-p-arg1663gly (accessed [today's date]).

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