Is MAPKAPK2 p.Ile271Val (c.811A>G) pathogenic?

MAPKAPK2 p.Ile271Val (c.811A>G) is classified Uncertain significance in MAPKAPK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). AlphaMissense: ambiguous (0.378); Very rare (popmax 0.000169%, nfe).

How common is MAPKAPK2 p.Ile271Val (c.811A>G) in the general population?

MAPKAPK2 p.Ile271Val (c.811A>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about MAPKAPK2 p.Ile271Val (c.811A>G)?

AlphaMissense predicts ambiguous (score 0.378) — an in-silico prediction, not a clinical call.

MAPKAPK2 p.Ile271Val

c.811A>G · VCV3543218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.378 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.378	ambiguous
REVEL	0.235	benign-leaning
SaProt	LLR -10.36	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.5, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 1,966 bp · p 4.2e-07 · regional, not allelic
Overall
CADD	24.3	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 0.000169% European (non-Finnish) · 2/1,179,990 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,966 alleles · very rare exomes 2/1,461,894 · genomes 0/152,072 · joint denominator

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: MAPKAPK2
Protein: p.Ile271Val
Coding: c.811A>G
MANE Select: NM_032960
Type: single nucleotide variant
Location: chr1:206731181 (GRCh38)
Gene constraint: LOEUF 0.303 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.08 · 31 PDB
Residue 271: the protein kinase domain

Full MAPKAPK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPKAPK2 p.Pro17= Likely benign ★★ same type
MAPKAPK2 p.Thr66= Benign ★★ same type
MAPKAPK2 p.Ala111Val Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Ala33Gly Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Ala378Gly Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Ala390Thr Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Arg110Trp Uncertain significance ★ ⚠ same type
MAPKAPK2 p.Arg119Gln 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/mapkapk2-p-ile271val (accessed [today's date]).

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