Is MAP3K11 p.Ser748Phe (c.2243C>T) pathogenic?

MAP3K11 p.Ser748Phe (c.2243C>T) is classified Uncertain significance in MAP3K11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-31). AlphaMissense: likely benign (0.1408); Very rare (popmax 0.000775%, nfe).

How common is MAP3K11 p.Ser748Phe (c.2243C>T) in the general population?

MAP3K11 p.Ser748Phe (c.2243C>T) is very rare (popmax 0.000775%, nfe) (gnomAD).

What do computational predictors say about MAP3K11 p.Ser748Phe (c.2243C>T)?

AlphaMissense predicts likely benign (score 0.1408) — an in-silico prediction, not a clinical call.

MAP3K11 p.Ser748Phe

c.2243C>T · rs372545474 · VCV2394189

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1408 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000775%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1408	likely benign
REVEL	0.297	indeterminate
SaProt	LLR -10.79	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 9,072 bp · p 0.49 · regional, not allelic
Overall
CADD	23.3	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 0.000775% European (non-Finnish) · 9/1,161,390 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000264%

Overall 0.000633% 10/1,579,042 alleles · very rare exomes 10/1,426,710 · genomes 0/152,332 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00164%	61,122
European (non-Finnish)grpmax	0.000775%	129,043

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MAP3K11
Protein: p.Ser748Phe
Coding: c.2243C>T
MANE Select: NM_002419
dbSNP: rs372545474
Type: single nucleotide variant
Location: chr11:65598592 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.79 · 4 PDB
Residue 748: a modified residue (phosphoserine); the 'disordered' region

Full MAP3K11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K11 p.Ala169Thr Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala282Pro Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala287Thr Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala352Ser Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala370Val Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala378Thr Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala39Gly Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala42Ser 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/map3k11-p-ser748phe (accessed [today's date]).

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