Is MYH9 p.Glu1663Asp (c.4989G>T) pathogenic?

MYH9 p.Glu1663Asp (c.4989G>T) is classified Benign in MYH9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.073); Ultra-rare (popmax 0.012%, afr).

How common is MYH9 p.Glu1663Asp (c.4989G>T) in the general population?

MYH9 p.Glu1663Asp (c.4989G>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about MYH9 p.Glu1663Asp (c.4989G>T)?

AlphaMissense predicts likely benign (score 0.073) — an in-silico prediction, not a clinical call.

MYH9 p.Glu1663Asp

c.4989G>T · VCV3712273

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.073 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.073	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -1.6, phastCons 0.99
Regional constraint	o/e 0.81	unconstrained · MANE · 12 kb · p 7.9e-10 · regional, not allelic
Overall
CADD	17.91	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 0.012% African / African-American · 9/74,944 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00062% 10/1,612,676 alleles · ultra-rare exomes 3/1,460,436 · genomes 7/152,240 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,327
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: MYH9
Protein: p.Glu1663Asp
Coding: c.4989G>T
MANE Select: NM_002473
Type: single nucleotide variant
Location: chr22:36286790 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 76.42 · 8 PDB

Full MYH9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MYH9 p.Ala95Thr Pathogenic/Likely pathogenic ★★ same type
MYH9 p.Arg1165Cys Pathogenic ★★ same type
MYH9 p.Arg1933Ter Pathogenic ★★ same type
MYH9 p.Arg702Cys Pathogenic ★★ same type
MYH9 p.Arg702Gly Pathogenic/Likely pathogenic ★★ same type
MYH9 p.Arg702His Pathogenic/Likely pathogenic ★★ same type
MYH9 p.Arg705His Pathogenic/Likely pathogenic ★★ same type
MYH9 p.Arg718Trp 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/myh9-p-glu1663asp (accessed [today's date]).

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