Is MYH9 p.Ile1626Val (c.4876A>G) pathogenic?

MYH9 p.Ile1626Val (c.4876A>G) is classified Benign in MYH9 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0866); Common (popmax 60.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with MYH9-related disorder.

What do computational predictors say about MYH9 p.Ile1626Val (c.4876A>G)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

MYH9 p.Ile1626Val

Q: What condition is associated with MYH9 p.Ile1626Val (c.4876A>G)?

MYH9 p.Ile1626Val (c.4876A>G) is associated with MYH9-related disorder, autosomal dominant nonsyndromic hearing loss 17, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (ClinVar).

Q: How common is MYH9 p.Ile1626Val (c.4876A>G) in the general population?

MYH9 p.Ile1626Val (c.4876A>G) is common (popmax 60.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4876A>G · rs2269529 · VCV38967

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 60.9%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYH9-related disorder

Computational evidence

Protein change
AlphaMissense	0.0866	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -5.95	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 0.93	GERP 2, phastCons 0.95
Regional constraint	o/e 0.81	unconstrained · MANE · 12 kb · p 7.9e-10 · regional, not allelic
Overall
CADD	19.8	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 60.9% East Asian · 27,272/44,810 alleles

Filtering AF 60.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 60%

Overall 21.9% 353,815/1,613,510 alleles · common exomes 324,972/1,461,550 · genomes 28,843/151,960 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	60.9%	2
South Asian	43.4%	2
Ashkenazi Jewishnot grpmax-eligible	35%	3
Admixed American	27.3%	4
Middle Eastern	26.7%	4
Remaining individualsnot grpmax-eligible	24.7%	4
European (non-Finnish)	19.2%	5
Amishnot grpmax-eligible	17.7%	6
Finnishnot grpmax-eligible	17.5%	6
African / African-American	6.99%	14

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.Ile1626Val
Coding: c.4876A>G
MANE Select: NM_002473
dbSNP: rs2269529
Type: single nucleotide variant
Location: chr22:36288308 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 76.42 · 8 PDB
Residue 1626: a UniProt-annotated variant site (in)

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

Disease context

Also linked: autosomal dominant nonsyndromic hearing loss 17 macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

Similar variants

MYH9 p.Ile1626= Conflicting classifications of pathogenicity ★ same residue
MYH9 p.Ala95Thr Pathogenic/Likely pathogenic ★★ same condition
MYH9 p.Arg1165Cys Pathogenic ★★ same condition
MYH9 p.Arg1933Ter Pathogenic ★★ same condition
MYH9 p.Arg702Cys Pathogenic ★★ same condition
MYH9 p.Arg702Gly Pathogenic/Likely pathogenic ★★ same condition
MYH9 p.Arg702His Pathogenic/Likely pathogenic ★★ same condition
MYH9 p.Arg705His Pathogenic/Likely pathogenic ★★ 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/myh9-p-ile1626val (accessed [today's date]).

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