Is MAP3K20 p.Ile141Val (c.421A>G) pathogenic?

MAP3K20 p.Ile141Val (c.421A>G) is classified Uncertain significance in MAP3K20 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). AlphaMissense: likely benign (0.1108); Very rare (popmax 0.00136%, afr).

How common is MAP3K20 p.Ile141Val (c.421A>G) in the general population?

MAP3K20 p.Ile141Val (c.421A>G) is very rare (popmax 0.00136%, afr) (gnomAD).

What do computational predictors say about MAP3K20 p.Ile141Val (c.421A>G)?

AlphaMissense predicts likely benign (score 0.1108) — an in-silico prediction, not a clinical call.

MAP3K20 p.Ile141Val

c.421A>G · rs373719708 · VCV1955584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1108 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1108	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -7.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 119 kb · p 3.5e-09 · regional, not allelic
Overall
CADD	20.4	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

Grpmax group 0.00136% African / African-American · 1/73,750 alleles

Filtering AF 0.000185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.000502% 8/1,593,594 alleles · very rare exomes 7/1,441,438 · genomes 1/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00136%	73,750
South Asian	0.00112%	89,122
European (non-Finnish)	0.000515%	194,225

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: MAP3K20
Protein: p.Ile141Val
Coding: c.421A>G
MANE Select: NM_016653
dbSNP: rs373719708
Type: single nucleotide variant
Location: chr2:173190900 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 69.15 · 8 PDB
Residue 141: the protein kinase domain; a UniProt-annotated variant site (in cnm6; decrease of protein abundance); a β-strand

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

Similar variants

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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-ile141val (accessed [today's date]).

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