Is MYH14 p.Arg1663Gln (c.4988G>A) pathogenic?

MYH14 p.Arg1663Gln (c.4988G>A) is classified Uncertain significance in MYH14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely benign (0.1509); Ultra-rare (popmax 0.0434%, sas); Associated with Inborn genetic diseases.

What condition is associated with MYH14 p.Arg1663Gln (c.4988G>A)?

MYH14 p.Arg1663Gln (c.4988G>A) is associated with Inborn genetic diseases (ClinVar).

How common is MYH14 p.Arg1663Gln (c.4988G>A) in the general population?

MYH14 p.Arg1663Gln (c.4988G>A) is ultra-rare (popmax 0.0434%, sas) (gnomAD).

What do computational predictors say about MYH14 p.Arg1663Gln (c.4988G>A)?

AlphaMissense predicts likely benign (score 0.1509) — an in-silico prediction, not a clinical call.

MYH14 p.Arg1663Gln

c.4988G>A · rs773412410 · VCV3156920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1509 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0434%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1509	likely benign
REVEL	0.369	indeterminate
SaProt	LLR -9.43	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP -3.7
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1622Q vs ClinVar R1663Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0434% South Asian · 37/85,210 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0285%

Overall 0.00382% 60/1,568,892 alleles · ultra-rare exomes 57/1,416,700 · genomes 3/152,192 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0434%	2,303
East Asian	0.0375%	2,664
Admixed American	0.00379%	26,363
European (non-Finnish)	0.000432%	231,556

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.Arg1663Gln
Coding: c.4988G>A
MANE Select: NM_001145809
dbSNP: rs773412410
Type: single nucleotide variant
Location: chr19:50290909 (GRCh38)
Structure: AlphaFold pLDDT 73.79

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYH14 p.Arg1663Trp Uncertain significance ★ ⚠ same residue
MYH14 p.Ala1023Val Uncertain significance ★★ ⚠ same condition
MYH14 p.Ala1267Ser Uncertain significance ★★ ⚠ same condition
MYH14 p.Ala1401Val Uncertain significance ★★ ⚠ same condition
MYH14 p.Ala1444Thr Uncertain significance ★★ ⚠ same condition
MYH14 p.Ala1629Ser Uncertain significance ★★ ⚠ same condition
MYH14 p.Ala422Gly Uncertain significance ★★ ⚠ same condition
MYH14 p.Ala615Ser Uncertain significance ★★ ⚠ 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/myh14-p-arg1663gln (accessed [today's date]).

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