Is MAP2K7 p.Ile310Val (c.928A>G) pathogenic?

MAP2K7 p.Ile310Val (c.928A>G) is classified Uncertain significance in MAP2K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-23). AlphaMissense: likely pathogenic (0.6688); Absent from gnomAD v4.1.

How common is MAP2K7 p.Ile310Val (c.928A>G) in the general population?

MAP2K7 p.Ile310Val (c.928A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP2K7 p.Ile310Val (c.928A>G)?

AlphaMissense predicts likely pathogenic (score 0.6688) — an in-silico prediction, not a clinical call.

MAP2K7 p.Ile310Val

c.928A>G · rs2512356417 · VCV2528913

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6688 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6688	likely pathogenic
REVEL	0.153	moderately benign-leaning
SaProt	LLR -10.53	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 1,458 bp · p 2.3e-17 · regional, not allelic
Overall
CADD	24.1	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: MAP2K7
Protein: p.Ile310Val
Coding: c.928A>G
MANE Select: NM_145185
dbSNP: rs2512356417
Type: single nucleotide variant
Location: chr19:7911322 (GRCh38)
Gene constraint: LOEUF 0.454 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 37 PDB
Residue 310: the protein kinase domain; an α-helix

Full MAP2K7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP2K7 c.855+10G>C Benign ★★ same type
MAP2K7 c.856-19T>C Benign ★★ same type
MAP2K7 c.856-8C>G Benign ★★ same type
MAP2K7 p.Cys131= Benign ★★ same type
MAP2K7 p.Pro215= Benign ★★ same type
MAP2K7 p.Ser277= Benign ★★ same type
MAP2K7 p.Ala391Val Uncertain significance ★ same type
MAP2K7 p.Ala399Val 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/map2k7-p-ile310val (accessed [today's date]).

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