Is MAP2K1 p.Ile174Val (c.520A>G) pathogenic?

MAP2K1 p.Ile174Val (c.520A>G) is classified Uncertain significance in MAP2K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-31). AlphaMissense: likely benign (0.1156); No allele count reported in gnomAD v4.1 (AN 1,607,680).

How common is MAP2K1 p.Ile174Val (c.520A>G) in the general population?

MAP2K1 p.Ile174Val (c.520A>G) is no allele count reported in gnomAD v4.1 (AN 1,607,680) (gnomAD).

What do computational predictors say about MAP2K1 p.Ile174Val (c.520A>G)?

AlphaMissense predicts likely benign (score 0.1156) — an in-silico prediction, not a clinical call.

MAP2K1 p.Ile174Val

c.520A>G · rs1891814988 · VCV1189400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1156 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,680)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1156	likely benign
REVEL	0.179	moderately benign-leaning
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.37	acceptor gain · deltas
Pangolin	Δ0.24	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 94 kb · p 1.7e-15 · regional, not allelic
Overall
CADD	25.4	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

No allele count reported in gnomAD v4.1 (AN 1,607,680). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAP2K1
Protein: p.Ile174Val
Coding: c.520A>G
MANE Select: NM_002755
dbSNP: rs1891814988
Type: single nucleotide variant
Location: chr15:66444659 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.97 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.05 · 99 PDB
Residue 174: the protein kinase domain; an α-helix

Full MAP2K1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP2K1 p.Arg108Leu Likely pathogenic ★★★ same type
MAP2K1 p.Asn122Asp Pathogenic ★★★ ⚠ same type
MAP2K1 p.Asp67Asn Pathogenic ★★★ same type
MAP2K1 p.Glu203Gly Pathogenic ★★★ same type
MAP2K1 p.Leu42Arg Likely pathogenic ★★★ same type
MAP2K1 p.Leu42Phe Pathogenic ★★★ same type
MAP2K1 p.Leu92Arg Pathogenic ★★★ same type
MAP2K1 p.Lys57Gln Likely pathogenic ★★★ 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/map2k1-p-ile174val (accessed [today's date]).

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