Is MAP3K20 p.Ser781Phe (c.2342C>T) pathogenic?

MAP3K20 p.Ser781Phe (c.2342C>T) is classified Uncertain significance in MAP3K20 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-18). AlphaMissense: likely benign (0.0758); Ultra-rare (popmax 0.0149%, nfe).

How common is MAP3K20 p.Ser781Phe (c.2342C>T) in the general population?

MAP3K20 p.Ser781Phe (c.2342C>T) is ultra-rare (popmax 0.0149%, nfe) (gnomAD).

What do computational predictors say about MAP3K20 p.Ser781Phe (c.2342C>T)?

AlphaMissense predicts likely benign (score 0.0758) — an in-silico prediction, not a clinical call.

MAP3K20 p.Ser781Phe

c.2342C>T · rs202237846 · VCV1507203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0758 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0149%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0758	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -8.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.7	GERP 1.9, phastCons 0.004
Regional constraint	o/e 0.95	unconstrained · MANE · 28 kb · p 0.29 · regional, not allelic
Overall
CADD	17.09	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 0.0149% European (non-Finnish) · 175/1,172,654 alleles

Filtering AF 0.0131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.0113% 181/1,598,454 alleles · ultra-rare exomes 172/1,446,810 · genomes 9/151,644 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0149%	6,701
Remaining individualsnot grpmax-eligible	0.00648%	15,435
African / African-American	0.0027%	37,066

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.Ser781Phe
Coding: c.2342C>T
MANE Select: NM_016653
dbSNP: rs202237846
Type: single nucleotide variant
Location: chr2:173266689 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 69.15 · 8 PDB
Residue 781: a UniProt-annotated variant site (in cnm6; decrease of protein abundance); the 'disordered' region; the 'c-terminal domain (ctd)' region

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-ser781phe (accessed [today's date]).

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