Is MAP4K2 p.Ala120Ser (c.358G>T) pathogenic?

MAP4K2 p.Ala120Ser (c.358G>T) is classified Benign in MAP4K2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-18). AlphaMissense: likely benign (0.196); Low-frequency (popmax 2.94%, mid).

How common is MAP4K2 p.Ala120Ser (c.358G>T) in the general population?

MAP4K2 p.Ala120Ser (c.358G>T) is low-frequency (popmax 2.94%, mid) (gnomAD).

What do computational predictors say about MAP4K2 p.Ala120Ser (c.358G>T)?

AlphaMissense predicts likely benign (score 0.196) — an in-silico prediction, not a clinical call.

MAP4K2 p.Ala120Ser

c.358G>T · rs115646677 · VCV776624

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.196 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.94%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.196	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -6.39	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 7.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 13 kb · p 0.0094 · regional, not allelic
Overall
CADD	23.6	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 2.94% Middle Eastern · 168/5,724 alleles

Filtering AF 2.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.43%

Overall 0.733% 11,814/1,612,492 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.94%	34
African / African-American	2.34%	43
Ashkenazi Jewishnot grpmax-eligible	1.71%	59
Remaining individualsnot grpmax-eligible	0.971%	103
Admixed American	0.954%	105
Amishnot grpmax-eligible	0.659%	152
European (non-Finnish)	0.642%	156
South Asian	0.586%	171
Finnishnot grpmax-eligible	0.138%	726
East Asian	0.00446%	22,437

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: MAP4K2
Protein: p.Ala120Ser
Coding: c.358G>T
MANE Select: NM_004579
dbSNP: rs115646677
Type: single nucleotide variant
Location: chr11:64802074 (GRCh38)
Gene constraint: LOEUF 0.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.32
Residue 120: the protein kinase domain

Full MAP4K2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP4K2 p.Asn606= Benign ★★ same type
MAP4K2 p.Ala183Asp Uncertain significance ★ ⚠ same type
MAP4K2 p.Ala184Ser Uncertain significance ★ same type
MAP4K2 p.Ala405Thr Uncertain significance ★ ⚠ same type
MAP4K2 p.Ala487Thr Uncertain significance ★ ⚠ same type
MAP4K2 p.Ala790Asp Uncertain significance ★ ⚠ same type
MAP4K2 p.Ala806Val Uncertain significance ★ same type
MAP4K2 p.Arg111Gln 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/map4k2-p-ala120ser (accessed [today's date]).

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