Is MAP3K20 p.Ser424del (c.1270_1272del) pathogenic?

MAP3K20 p.Ser424del (c.12701272del) is classified Uncertain significance in MAP3K20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-05). Very rare (popmax 0.00843%, amr).

How common is MAP3K20 p.Ser424del (c.1270_1272del) in the general population?

MAP3K20 p.Ser424del (c.1270_1272del) is very rare (popmax 0.00843%, amr) (gnomAD).

MAP3K20 p.Ser424del

c.1270_1272del · rs753352140 · VCV1389623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00843%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.07	GERP -0.11, phastCons 0.92
Overall
CADD	15.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00843% Admixed American · 5/59,308 alleles

Filtering AF 0.00326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00209%

Overall 0.000497% 8/1,610,722 alleles · very rare exomes 2/1,459,276 · genomes 6/151,446 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00843%	11,862
African / African-American	0.00268%	37,281
European (non-Finnish)	8.48e-05%	1,179,184

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.Ser424del
Coding: c.1270_1272del
MANE Select: NM_016653
dbSNP: rs753352140
Type: Deletion
Location: chr2:173239407 (GRCh38)
Gene constraint: LOEUF 0.569 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 69.15 · 8 PDB
Residue 424: 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 c.1360-14_1360-12del Likely benign ★★ same type
MAP3K20 c.1360-14_1360-9del Benign/Likely benign ★★ same type
MAP3K20 c.850_851+1del Likely pathogenic ★ same type
MAP3K20 p.Met164fs Pathogenic ★ same type
MAP3K20 p.Thr552_Leu553del Uncertain significance ★ same type
MAP3K20 c.1064-6del Likely benign ★ same type
MAP3K20 c.1360-10_1360-9del Likely benign ★ same type
MAP3K20 c.1360-11_1360-9del Likely benign ★ 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-ser424del (accessed [today's date]).

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