Is MAP3K11 p.Val237Ile (c.709G>A) pathogenic?

MAP3K11 p.Val237Ile (c.709G>A) is classified Uncertain significance in MAP3K11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: likely benign (0.1091); Ultra-rare (popmax 0.032%, eas).

How common is MAP3K11 p.Val237Ile (c.709G>A) in the general population?

MAP3K11 p.Val237Ile (c.709G>A) is ultra-rare (popmax 0.032%, eas) (gnomAD).

What do computational predictors say about MAP3K11 p.Val237Ile (c.709G>A)?

AlphaMissense predicts likely benign (score 0.1091) — an in-silico prediction, not a clinical call.

MAP3K11 p.Val237Ile

c.709G>A · VCV3293003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1091 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1091	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -2.40	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -3.5, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 6,022 bp · p 7.7e-13 · regional, not allelic
Overall
CADD	24.0	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% East Asian · 14/43,780 alleles

Filtering AF 0.0193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0154%

Overall 0.00138% 21/1,520,886 alleles · ultra-rare exomes 20/1,368,652 · genomes 1/152,234 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.032%	3,127
African / African-American	0.00417%	23,958
South Asian	0.00263%	38,058
European (non-Finnish)	0.000176%	567,572

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: MAP3K11
Protein: p.Val237Ile
Coding: c.709G>A
MANE Select: NM_002419
Type: single nucleotide variant
Location: chr11:65613048 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.79 · 4 PDB
Residue 237: the protein kinase domain

Full MAP3K11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K11 p.Ala169Thr Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala282Pro Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala287Thr Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala352Ser Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala370Val Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala378Thr Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala39Gly Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala42Ser 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/map3k11-p-val237ile (accessed [today's date]).

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