Is MAP3K20 p.Pro780= (c.2340A>G) pathogenic?

MAP3K20 p.Pro780= (c.2340A>G) is classified Likely benign in MAP3K20 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-15). Very rare (popmax 0.00997%, nfe).

How common is MAP3K20 p.Pro780= (c.2340A>G) in the general population?

MAP3K20 p.Pro780= (c.2340A>G) is very rare (popmax 0.00997%, nfe) (gnomAD).

MAP3K20 p.Pro780=

c.2340A>G · rs759816291 · VCV2175065

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00997%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.089	GERP -4.7
Overall
CADD	1.076	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00997% European (non-Finnish) · 117/1,172,992 alleles

Filtering AF 0.00847% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00792%

Overall 0.008% 128/1,599,392 alleles · very rare exomes 124/1,447,514 · genomes 4/151,878 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0146%	6,865
European (non-Finnish)grpmax	0.00997%	10,026
African / African-American	0.00269%	37,131

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro780=
Coding: c.2340A>G
MANE Select: NM_016653
dbSNP: rs759816291
Type: single nucleotide variant
Location: chr2:173266687 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 69.15 · 8 PDB
Residue 780: 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-pro780 (accessed [today's date]).

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