Is MYH14 p.Arg1663Trp (c.4987C>T) pathogenic?

MYH14 p.Arg1663Trp (c.4987C>T) is classified Uncertain significance in MYH14 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-24). AlphaMissense: likely benign (0.3189); Very rare (popmax 0.00588%, sas).

How common is MYH14 p.Arg1663Trp (c.4987C>T) in the general population?

MYH14 p.Arg1663Trp (c.4987C>T) is very rare (popmax 0.00588%, sas) (gnomAD).

What do computational predictors say about MYH14 p.Arg1663Trp (c.4987C>T)?

AlphaMissense predicts likely benign (score 0.3189) — an in-silico prediction, not a clinical call.

MYH14 p.Arg1663Trp

c.4987C>T · rs375795690 · VCV1050845

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3189 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00588%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3189	likely benign
REVEL	0.411	indeterminate
SaProt	LLR -10.91	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -0.16, phastCons 0.005
Overall
CADD	24.2	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 R1622W vs ClinVar R1663W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00588% South Asian · 5/85,066 alleles

Filtering AF 0.00222% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00145%

Overall 0.00236% 37/1,567,014 alleles · very rare exomes 35/1,414,868 · genomes 2/152,146 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00588%	17,013
Admixed American	0.00571%	17,513
Remaining individualsnot grpmax-eligible	0.00329%	30,355
East Asian	0.00235%	42,560
European (non-Finnish)	0.00225%	44,491

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: MYH14
Protein: p.Arg1663Trp
Coding: c.4987C>T
MANE Select: NM_001145809
dbSNP: rs375795690
Type: single nucleotide variant
Location: chr19:50290908 (GRCh38)
Structure: AlphaFold pLDDT 73.79

Full MYH14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MYH14 p.Arg1663Gln Uncertain significance ★ ⚠ same residue
MYH14 c.590+1G>A Pathogenic/Likely pathogenic ★★ same type
MYH14 p.Arg974Leu Pathogenic ★★ same type
MYH14 c.4966-2A>G Uncertain significance ★★ same type
MYH14 c.5345+6T>C Uncertain significance ★★ same type
MYH14 c.5787+5G>T Uncertain significance ★★ same type
MYH14 c.5960+4T>C Uncertain significance ★★ same type
MYH14 c.-3-6C>T 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/myh14-p-arg1663trp (accessed [today's date]).

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