Is MAPKAP1 p.Ile452Val (c.1354A>G) pathogenic?

MAPKAP1 p.Ile452Val (c.1354A>G) is classified Uncertain significance in MAPKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely benign (0.0612); Ultra-rare (popmax 0.0236%, nfe).

How common is MAPKAP1 p.Ile452Val (c.1354A>G) in the general population?

MAPKAP1 p.Ile452Val (c.1354A>G) is ultra-rare (popmax 0.0236%, nfe) (gnomAD).

What do computational predictors say about MAPKAP1 p.Ile452Val (c.1354A>G)?

AlphaMissense predicts likely benign (score 0.0612) — an in-silico prediction, not a clinical call.

MAPKAP1 p.Ile452Val

c.1354A>G · rs752861508 · VCV2351118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0612 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0236%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0612	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.28	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 6.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 104 kb · p 3.8e-07 · regional, not allelic
Overall
CADD	18.21	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 0.0236% European (non-Finnish) · 278/1,178,784 alleles

Filtering AF 0.0213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0204%

Overall 0.0182% 293/1,612,284 alleles · ultra-rare exomes 282/1,460,068 · genomes 11/152,216 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0236%	4,240
Remaining individualsnot grpmax-eligible	0.0112%	8,911
Admixed American	0.00669%	14,953
African / African-American	0.00401%	24,961
South Asian	0.0011%	90,954

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: MAPKAP1
Protein: p.Ile452Val
Coding: c.1354A>G
MANE Select: NM_001006617
dbSNP: rs752861508
Type: single nucleotide variant
Location: chr9:125444590 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.55 · 23 PDB
Residue 452: the sin1-type ph domain; a β-strand

Full MAPKAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPKAP1 p.Ser488= Benign ★★ same type
MAPKAP1 p.Ala201Thr Uncertain significance ★ ⚠ same type
MAPKAP1 p.Ala229Asp Uncertain significance ★ same type
MAPKAP1 p.Ala286Thr Uncertain significance ★ ⚠ same type
MAPKAP1 p.Arg15Gln Uncertain significance ★ ⚠ same type
MAPKAP1 p.Arg202Lys Uncertain significance ★ ⚠ same type
MAPKAP1 p.Arg503Ile Uncertain significance ★ ⚠ same type
MAPKAP1 p.Asn476Ser 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/mapkap1-p-ile452val (accessed [today's date]).

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