Is MAP3K20 p.Val9Ala (c.26T>C) pathogenic?

MAP3K20 p.Val9Ala (c.26T>C) is classified Uncertain significance in MAP3K20 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-13). AlphaMissense: likely pathogenic (0.7998); Very rare (popmax 0.00161%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MAP3K20 p.Val9Ala (c.26T>C)?

MAP3K20 p.Val9Ala (c.26T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MAP3K20 p.Val9Ala (c.26T>C) in the general population?

MAP3K20 p.Val9Ala (c.26T>C) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about MAP3K20 p.Val9Ala (c.26T>C)?

AlphaMissense predicts likely pathogenic (score 0.7998) — an in-silico prediction, not a clinical call.

MAP3K20 p.Val9Ala

c.26T>C · rs148183363 · VCV1897247

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7998 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7998	likely pathogenic
REVEL	0.744	pathogenic-leaning
SaProt	LLR -8.59	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 119 kb · p 3.5e-09 · regional, not allelic
Overall
CADD	28.2	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 0.00161% European (non-Finnish) · 19/1,179,970 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00118% 19/1,613,920 alleles · very rare exomes 18/1,461,764 · genomes 1/152,156 · joint denominator

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.Val9Ala
Coding: c.26T>C
MANE Select: NM_016653
dbSNP: rs148183363
Type: single nucleotide variant
Location: chr2:173091057 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 69.15 · 8 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP3K20 p.Arg536Lys Uncertain significance ★★ ⚠ same condition
MAP3K20 p.Glu405Gly Uncertain significance ★★ same condition
MAP3K20 p.Arg377Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
MAP3K20 p.Asn222Asp Uncertain significance ★ ⚠ same condition
MAP3K20 p.Arg250Trp Uncertain significance ★★ ⚠ same type
MAP3K20 p.Arg293Lys Uncertain significance ★★ same type
MAP3K20 p.Arg634Gly Uncertain significance ★★ ⚠ same type
MAP3K20 p.Arg774Trp 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-val9ala (accessed [today's date]).

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