Is MAP4K4 p.Ser1027Ala (c.3079T>G) pathogenic?

MAP4K4 p.Ser1027Ala (c.3079T>G) is classified Likely benign in MAP4K4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely benign (0.0835); Ultra-rare (popmax 0.0588%, afr); Associated with Inborn genetic diseases.

What condition is associated with MAP4K4 p.Ser1027Ala (c.3079T>G)?

MAP4K4 p.Ser1027Ala (c.3079T>G) is associated with Inborn genetic diseases (ClinVar).

How common is MAP4K4 p.Ser1027Ala (c.3079T>G) in the general population?

MAP4K4 p.Ser1027Ala (c.3079T>G) is ultra-rare (popmax 0.0588%, afr) (gnomAD).

What do computational predictors say about MAP4K4 p.Ser1027Ala (c.3079T>G)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

MAP4K4 p.Ser1027Ala

c.3079T>G · VCV3542997

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0588%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.137	moderately benign-leaning
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 18 kb · p 1e-07 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S882A vs ClinVar S1027A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0588% African / African-American · 44/74,874 alleles

Filtering AF 0.0449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0401%

Overall 0.00298% 48/1,612,800 alleles · ultra-rare exomes 20/1,460,612 · genomes 28/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0588%	1,702
Remaining individualsnot grpmax-eligible	0.00321%	31,200
Admixed American	0.00167%	59,916
South Asian	0.0011%	90,964

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: MAP4K4
Protein: p.Ser1027Ala
Coding: c.3079T>G
MANE Select: NM_001395002
Type: single nucleotide variant
Location: chr2:101874090 (GRCh38)
Gene constraint: LOEUF 0.308 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.47 · 19 PDB
Residue 882 UniProt numbering: the 'mediates interaction with rap2a' region

Full MAP4K4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP4K4 p.Arg1329Ter Pathogenic/Likely pathogenic ★★ same condition
MAP4K4 p.Ala491Pro Uncertain significance ★★ ⚠ same condition
MAP4K4 p.Leu742Pro Uncertain significance ★★ ⚠ same condition
MAP4K4 p.Ser758Phe Uncertain significance ★★ ⚠ same condition
MAP4K4 p.Asp203Gly Likely pathogenic ★ same condition
MAP4K4 p.Gln402Ter Pathogenic ★ same condition
MAP4K4 p.Gly173Asp Pathogenic ★ same condition
MAP4K4 p.Lys54Arg Likely pathogenic ★ same condition

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/map4k4-p-ser1027ala (accessed [today's date]).

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