Is MAP2K3 p.Val251Ile (c.751G>A) pathogenic?

MAP2K3 p.Val251Ile (c.751G>A) is classified Likely benign in MAP2K3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0944); Rare (popmax 0.205%, nfe).

How common is MAP2K3 p.Val251Ile (c.751G>A) in the general population?

MAP2K3 p.Val251Ile (c.751G>A) is rare (popmax 0.205%, nfe) (gnomAD).

What do computational predictors say about MAP2K3 p.Val251Ile (c.751G>A)?

AlphaMissense predicts likely benign (score 0.0944) — an in-silico prediction, not a clinical call.

MAP2K3 p.Val251Ile

c.751G>A · rs150613942 · VCV771765

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0944 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.205%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0944	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -8.69	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 5.2	GERP 0.073, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 7,613 bp · p 2.2e-11 · regional, not allelic
Overall
CADD	19.95	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 0.205% European (non-Finnish) · 2,410/1,177,868 alleles

Filtering AF 0.198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.173% 2,793/1,611,684 alleles · rare exomes 2,572/1,459,370 · genomes 221/152,314 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.205%	489
Remaining individualsnot grpmax-eligible	0.176%	567
South Asian	0.142%	704
Admixed American	0.112%	895
East Asian	0.0512%	1,952
Finnishnot grpmax-eligible	0.0375%	2,668
African / African-American	0.0373%	2,681
Middle Eastern	0.033%	3,029

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: MAP2K3
Protein: p.Val251Ile
Coding: c.751G>A
MANE Select: NM_145109
dbSNP: rs150613942
Type: single nucleotide variant
Location: chr17:21305105 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.13
Residue 251: the protein kinase domain

Full MAP2K3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP2K3 p.Leu215Trp Uncertain significance ★★ ⚠ same type
MAP2K3 c.568+10C>T Benign ★★ same type
MAP2K3 p.Ala220= Benign ★★ same type
MAP2K3 p.Ala225= Likely benign ★★ same type
MAP2K3 p.Leu25= Benign ★★ same type
MAP2K3 p.Leu319= Likely benign ★★ same type
MAP2K3 p.Pro40Thr Benign ★★ same type
MAP2K3 p.Ser286= Likely benign ★★ 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/map2k3-p-val251ile (accessed [today's date]).

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