Is MAP3K7 p.Ser8Ala (c.22T>G) pathogenic?

MAP3K7 p.Ser8Ala (c.22T>G) is classified Conflicting classifications of pathogenicity in MAP3K7 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-12). AlphaMissense: likely benign (0.0553); Ultra-rare (popmax 0.0419%, amr).

How common is MAP3K7 p.Ser8Ala (c.22T>G) in the general population?

MAP3K7 p.Ser8Ala (c.22T>G) is ultra-rare (popmax 0.0419%, amr) (gnomAD).

What do computational predictors say about MAP3K7 p.Ser8Ala (c.22T>G)?

AlphaMissense predicts likely benign (score 0.0553) — an in-silico prediction, not a clinical call.

MAP3K7 p.Ser8Ala

c.22T>G · rs766181895 · VCV2082557

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0553 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0419%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0553	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -7.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 102 bp · p 0.95 · regional, not allelic
Overall
CADD	21.6	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 0.0419% Admixed American · 25/59,694 alleles

Filtering AF 0.029% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00528% 85/1,610,078 alleles · ultra-rare exomes 67/1,457,896 · genomes 18/152,182 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0419%	2,388
Remaining individualsnot grpmax-eligible	0.0193%	5,187
African / African-American	0.00537%	18,619
European (non-Finnish)	0.00365%	27,403
South Asian	0.0011%	90,968

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: MAP3K7
Protein: p.Ser8Ala
Coding: c.22T>G
MANE Select: NM_145331
dbSNP: rs766181895
Type: single nucleotide variant
Location: chr6:90586862 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.27 · 25 PDB
Residue 8: the 'interaction with mapk8ip1' region

Full MAP3K7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K7 p.Arg274Cys Pathogenic/Likely pathogenic ★★ same type
MAP3K7 p.Gly110Ser Pathogenic/Likely pathogenic ★★ same type
MAP3K7 p.Pro512Leu Pathogenic ★★ same type
MAP3K7 p.Ala313Thr Uncertain significance ★★ ⚠ same type
MAP3K7 p.Ala400Thr Uncertain significance ★★ ⚠ same type
MAP3K7 p.Ala6Thr Uncertain significance ★★ ⚠ same type
MAP3K7 p.Arg289Gln Uncertain significance ★★ ⚠ same type
MAP3K7 p.Arg347His 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/map3k7-p-ser8ala (accessed [today's date]).

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