Is MAP3K20 p.Thr374= (c.1122A>G) pathogenic?

MAP3K20 p.Thr374= (c.1122A>G) is classified Benign in MAP3K20 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Common (popmax 57.5%, eas) — too common for a highly-penetrant pathogenic allele.

MAP3K20 p.Thr374=

Q: How common is MAP3K20 p.Thr374= (c.1122A>G) in the general population?

MAP3K20 p.Thr374= (c.1122A>G) is common (popmax 57.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1122A>G · rs16861406 · VCV1233130

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 57.5%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -5.8
Overall
CADD	2.939	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 57.5% East Asian · 25,810/44,880 alleles

Filtering AF 56.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 56.7%

Overall 8.97% 144,804/1,614,180 alleles · common exomes 129,975/1,461,884 · genomes 14,829/152,296 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	57.5%	2
Admixed American	16.8%	6
Finnishnot grpmax-eligible	10.5%	10
Remaining individualsnot grpmax-eligible	10.4%	10
Ashkenazi Jewishnot grpmax-eligible	10.3%	10
South Asian	7.84%	13
Middle Eastern	7.16%	14
European (non-Finnish)	6.8%	15
Amishnot grpmax-eligible	6.37%	16
African / African-American	6.35%	16

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.Thr374=
Coding: c.1122A>G
MANE Select: NM_016653
dbSNP: rs16861406
Type: single nucleotide variant
Location: chr2:173232378 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 69.15 · 8 PDB
Residue 374: the sam domain; 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-thr374 (accessed [today's date]).

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