Is MAP3K11 p.Pro3Leu (c.8C>T) pathogenic?

MAP3K11 p.Pro3Leu (c.8C>T) is classified Uncertain significance in MAP3K11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-09). AlphaMissense: likely pathogenic (0.7842); Absent from gnomAD v4.1.

How common is MAP3K11 p.Pro3Leu (c.8C>T) in the general population?

MAP3K11 p.Pro3Leu (c.8C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K11 p.Pro3Leu (c.8C>T)?

AlphaMissense predicts likely pathogenic (score 0.7842) — an in-silico prediction, not a clinical call.

MAP3K11 p.Pro3Leu

c.8C>T · VCV4051251

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7842 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7842	likely pathogenic
REVEL	0.316	indeterminate
SaProt	LLR -5.41	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 366 bp · p 0.57 · regional, not allelic
Overall
CADD	27.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAP3K11
Protein: p.Pro3Leu
Coding: c.8C>T
MANE Select: NM_002419
Type: single nucleotide variant
Location: chr11:65613749 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.79 · 4 PDB

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-pro3leu (accessed [today's date]).

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