Is MAP3K20 p.Val615Leu (c.1843G>T) pathogenic?

MAP3K20 p.Val615Leu (c.1843G>T) is classified Likely benign in MAP3K20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). AlphaMissense: likely benign (0.2774); Ultra-rare (popmax 0.0813%, afr).

How common is MAP3K20 p.Val615Leu (c.1843G>T) in the general population?

MAP3K20 p.Val615Leu (c.1843G>T) is ultra-rare (popmax 0.0813%, afr) (gnomAD).

What do computational predictors say about MAP3K20 p.Val615Leu (c.1843G>T)?

AlphaMissense predicts likely benign (score 0.2774) — an in-silico prediction, not a clinical call.

MAP3K20 p.Val615Leu

c.1843G>T · rs200821510 · VCV1423792

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2774 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0813%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2774	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 28 kb · p 0.29 · regional, not allelic
Overall
CADD	24.1	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 0.0813% African / African-American · 61/75,028 alleles

Filtering AF 0.0649% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.059%

Overall 0.00564% 91/1,614,100 alleles · ultra-rare exomes 42/1,461,850 · genomes 49/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0813%	1,230
Middle Eastern	0.033%	3,031
Admixed American	0.03%	3,334
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	0.000169%	590,005

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.Val615Leu
Coding: c.1843G>T
MANE Select: NM_016653
dbSNP: rs200821510
Type: single nucleotide variant
Location: chr2:173266190 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 69.15 · 8 PDB
Residue 615: a UniProt-annotated variant site (in cnm6; decrease of protein abundance)

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-val615leu (accessed [today's date]).

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