Is MAP4K1 p.Ser797Phe (c.2390C>T) pathogenic?

MAP4K1 p.Ser797Phe (c.2390C>T) is classified Uncertain significance in MAP4K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.154); Very rare (popmax 0.000424%, nfe).

How common is MAP4K1 p.Ser797Phe (c.2390C>T) in the general population?

MAP4K1 p.Ser797Phe (c.2390C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about MAP4K1 p.Ser797Phe (c.2390C>T)?

AlphaMissense predicts likely benign (score 0.154) — an in-silico prediction, not a clinical call.

MAP4K1 p.Ser797Phe

c.2390C>T · VCV4103512

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.154 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.154	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -8.66	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 3.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 9,773 bp · p 0.0018 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,050 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000343% 5/1,459,802 alleles · very rare

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: MAP4K1
Protein: p.Ser797Phe
Coding: c.2390C>T
MANE Select: NM_001042600
Type: single nucleotide variant
Location: chr19:38593288 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.83 · 50 PDB
Residue 797: the cnh domain

Full MAP4K1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP4K1 p.Ala246Ser Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala313Pro Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala452Ser Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala452Thr Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala452Val Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala485Ser Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala609Val Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala661Gly 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/map4k1-p-ser797phe (accessed [today's date]).

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