Is MAP3K7 p.Pro271Ala (c.811C>G) pathogenic?

MAP3K7 p.Pro271Ala (c.811C>G) is classified Uncertain significance in MAP3K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: ambiguous (0.3932); Absent from gnomAD v4.1.

How common is MAP3K7 p.Pro271Ala (c.811C>G) in the general population?

MAP3K7 p.Pro271Ala (c.811C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K7 p.Pro271Ala (c.811C>G)?

AlphaMissense predicts ambiguous (score 0.3932) — an in-silico prediction, not a clinical call.

MAP3K7 p.Pro271Ala

c.811C>G · VCV3369873

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3932 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3932	ambiguous
REVEL	0.484	indeterminate
SaProt	LLR -9.87	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 33 kb · p 0.12 · regional, not allelic
Overall
CADD	29.0	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: MAP3K7
Protein: p.Pro271Ala
Coding: c.811C>G
MANE Select: NM_145331
Type: single nucleotide variant
Location: chr6:90552105 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.27 · 25 PDB
Residue 271: the protein kinase domain; the 'interaction with mapk8ip1' region; an α-helix

Full MAP3K7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K7 p.Arg274Cys Pathogenic/Likely pathogenic ★★ same type
MAP3K7 p.Gly110Ser Pathogenic/Likely pathogenic ★★ same type
MAP3K7 p.Pro512Leu Pathogenic ★★ same type
MAP3K7 p.Ala313Thr Uncertain significance ★★ ⚠ same type
MAP3K7 p.Ala400Thr Uncertain significance ★★ ⚠ same type
MAP3K7 p.Ala6Thr Uncertain significance ★★ ⚠ same type
MAP3K7 p.Arg289Gln Uncertain significance ★★ ⚠ same type
MAP3K7 p.Arg347His 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/map3k7-p-pro271ala (accessed [today's date]).

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