Is MAP3K20 p.Pro228Ser (c.682C>T) pathogenic?

MAP3K20 p.Pro228Ser (c.682C>T) is classified Uncertain significance in MAP3K20 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). AlphaMissense: likely pathogenic (0.9983); Absent from gnomAD v4.1.

How common is MAP3K20 p.Pro228Ser (c.682C>T) in the general population?

MAP3K20 p.Pro228Ser (c.682C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K20 p.Pro228Ser (c.682C>T)?

AlphaMissense predicts likely pathogenic (score 0.9983) — an in-silico prediction, not a clinical call.

MAP3K20 p.Pro228Ser

c.682C>T · rs2468183324 · VCV2020951

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9983 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9983	likely pathogenic · top 4% in MAP3K20
REVEL	0.799	moderately pathogenic-leaning
SaProt	LLR -12.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 119 kb · p 3.5e-09 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: MAP3K20
Protein: p.Pro228Ser
Coding: c.682C>T
MANE Select: NM_016653
dbSNP: rs2468183324
Type: single nucleotide variant
Location: chr2:173203808 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 69.15 · 8 PDB
Residue 228: the protein kinase domain; a UniProt-annotated variant site (in cnm6; decrease of protein abundance); an α-helix

Full MAP3K20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K20 p.Arg250Trp Uncertain significance ★★ ⚠ same type
MAP3K20 p.Arg293Lys Uncertain significance ★★ same type
MAP3K20 p.Arg536Lys Uncertain significance ★★ ⚠ same type
MAP3K20 p.Arg634Gly Uncertain significance ★★ ⚠ same type
MAP3K20 p.Arg774Trp Uncertain significance ★★ ⚠ same type
MAP3K20 p.Arg795His Uncertain significance ★★ ⚠ same type
MAP3K20 p.Gln632Ter Uncertain significance ★★ same type
MAP3K20 p.Glu405Gly 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/map3k20-p-pro228ser (accessed [today's date]).

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