Is MAP3K12 p.Pro54Leu (c.161C>T) pathogenic?

MAP3K12 p.Pro54Leu (c.161C>T) is classified Uncertain significance in MAP3K12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). Absent from gnomAD v4.1.

How common is MAP3K12 p.Pro54Leu (c.161C>T) in the general population?

MAP3K12 p.Pro54Leu (c.161C>T) is absent from gnomAD v4.1 (gnomAD).

MAP3K12 p.Pro54Leu

c.161C>T · VCV3542784

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.292	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.43 · evaluated, not missing
Pangolin	Δ0.26	gain · loss 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 352 bp · p 0.18 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

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: MAP3K12
Protein: p.Pro54Leu
Coding: c.161C>T
MANE Select: NM_001193511
Type: single nucleotide variant
Location: chr12:53487231 (GRCh38)
Gene constraint: LOEUF 0.247 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.80 · 12 PDB
Residue 54: the 'disordered' region

Full MAP3K12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K12 p.Gly661Arg Uncertain significance ★★ ⚠ same type
MAP3K12 p.Gly673Ser Benign ★★ same type
MAP3K12 p.Ala671Asp Uncertain significance ★ ⚠ same type
MAP3K12 p.Arg106Gln Uncertain significance ★ ⚠ same type
MAP3K12 p.Arg176Cys Uncertain significance ★ ⚠ same type
MAP3K12 p.Arg236Trp Uncertain significance ★ ⚠ same type
MAP3K12 p.Arg488Lys Uncertain significance ★ ⚠ same type
MAP3K12 p.Arg572Gln 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/map3k12-p-pro54leu (accessed [today's date]).

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