Is MAPKAP1 p.Glu159Lys (c.475G>A) pathogenic?

MAPKAP1 p.Glu159Lys (c.475G>A) is classified Uncertain significance in MAPKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely pathogenic (0.6649); Very rare (popmax 0.00127%, nfe).

How common is MAPKAP1 p.Glu159Lys (c.475G>A) in the general population?

MAPKAP1 p.Glu159Lys (c.475G>A) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about MAPKAP1 p.Glu159Lys (c.475G>A)?

AlphaMissense predicts likely pathogenic (score 0.6649) — an in-silico prediction, not a clinical call.

MAPKAP1 p.Glu159Lys

c.475G>A · VCV4051670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6649 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6649	likely pathogenic
REVEL	0.419	indeterminate
SaProt	LLR -8.33	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 115 kb · p 4.5e-13 · 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 0.00127% European (non-Finnish) · 15/1,178,454 alleles

Filtering AF 0.000764% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000606%

Overall 0.000932% 15/1,609,020 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: MAPKAP1
Protein: p.Glu159Lys
Coding: c.475G>A
MANE Select: NM_001006617
Type: single nucleotide variant
Location: chr9:125657674 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.55 · 23 PDB
Residue 159: the crim domain; the 'interaction with nbn' region; the 'interaction with map3k2' region

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-glu159lys (accessed [today's date]).

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