Is MAP2K3 p.Ile52Thr (c.155T>C) pathogenic?

MAP2K3 p.Ile52Thr (c.155T>C) is classified Benign in MAP2K3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-26). AlphaMissense: ambiguous (0.5505); Rare (popmax 0.267%, amr).

How common is MAP2K3 p.Ile52Thr (c.155T>C) in the general population?

MAP2K3 p.Ile52Thr (c.155T>C) is rare (popmax 0.267%, amr) (gnomAD).

What do computational predictors say about MAP2K3 p.Ile52Thr (c.155T>C)?

AlphaMissense predicts ambiguous (score 0.5505) — an in-silico prediction, not a clinical call.

MAP2K3 p.Ile52Thr

c.155T>C · rs187946780 · VCV712987

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5505 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.267%, amr)

Computational evidence

Protein change
AlphaMissense	0.5505	ambiguous
REVEL	0.451	indeterminate
SaProt	LLR -13.39	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 20 kb · p 0.26 · regional, not allelic
Overall
CADD	26.5	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 0.267% Admixed American · 158/59,214 alleles

Filtering AF 0.233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.22%

Overall 0.0151% 244/1,613,344 alleles · rare exomes 192/1,460,930 · genomes 52/152,414 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.267%	375
East Asian	0.138%	723
Remaining individualsnot grpmax-eligible	0.0112%	8,929
African / African-American	0.00932%	10,726
European (non-Finnish)	0.000847%	118,003

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: MAP2K3
Protein: p.Ile52Thr
Coding: c.155T>C
MANE Select: NM_145109
dbSNP: rs187946780
Type: single nucleotide variant
Location: chr17:21298916 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.13

Full MAP2K3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP2K3 p.Leu215Trp Uncertain significance ★★ ⚠ same type
MAP2K3 c.568+10C>T Benign ★★ same type
MAP2K3 p.Ala220= Benign ★★ same type
MAP2K3 p.Ala225= Likely benign ★★ same type
MAP2K3 p.Leu25= Benign ★★ same type
MAP2K3 p.Leu319= Likely benign ★★ same type
MAP2K3 p.Pro40Thr Benign ★★ same type
MAP2K3 p.Ser286= Likely benign ★★ 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/map2k3-p-ile52thr (accessed [today's date]).

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