Is MAP2K7 p.Ala391Val (c.1172C>T) pathogenic?

MAP2K7 p.Ala391Val (c.1172C>T) is classified Uncertain significance in MAP2K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: ambiguous (0.5536); Very rare (popmax 0.00133%, afr).

How common is MAP2K7 p.Ala391Val (c.1172C>T) in the general population?

MAP2K7 p.Ala391Val (c.1172C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about MAP2K7 p.Ala391Val (c.1172C>T)?

AlphaMissense predicts ambiguous (score 0.5536) — an in-silico prediction, not a clinical call.

MAP2K7 p.Ala391Val

c.1172C>T · VCV3292980

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5536 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
AlphaMissense	0.5536	ambiguous
REVEL	0.434	indeterminate
SaProt	LLR -7.71	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 906 bp · p 0.27 · regional, not allelic
Overall
CADD	25.6	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 0.00133% African / African-American · 1/75,060 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,550 alleles · very rare exomes 4/1,461,238 · genomes 0/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,060
European (non-Finnish)	0.000254%	393,331

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: MAP2K7
Protein: p.Ala391Val
Coding: c.1172C>T
MANE Select: NM_145185
Type: single nucleotide variant
Location: chr19:7912343 (GRCh38)
Gene constraint: LOEUF 0.454 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.94 · 37 PDB
Residue 391: the 'dvd domain' region; 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.Ala399Val Uncertain significance ★ ⚠ same type
MAP2K7 p.Arg12Leu 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-ala391val (accessed [today's date]).

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