Is MAPKAP1 p.Ala229Asp (c.686C>A) pathogenic?

MAPKAP1 p.Ala229Asp (c.686C>A) is classified Uncertain significance in MAPKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: ambiguous (0.4389); Absent from gnomAD v4.1.

How common is MAPKAP1 p.Ala229Asp (c.686C>A) in the general population?

MAPKAP1 p.Ala229Asp (c.686C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPKAP1 p.Ala229Asp (c.686C>A)?

AlphaMissense predicts ambiguous (score 0.4389) — an in-silico prediction, not a clinical call.

MAPKAP1 p.Ala229Asp

c.686C>A · VCV3870506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4389 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4389	ambiguous
REVEL	0.361	indeterminate
SaProt	LLR -5.65	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 115 kb · p 4.5e-13 · regional, not allelic
Overall
CADD	24.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAPKAP1
Protein: p.Ala229Asp
Coding: c.686C>A
MANE Select: NM_001006617
Type: single nucleotide variant
Location: chr9:125559795 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.55 · 23 PDB
Residue 229: the crim domain; the 'interaction with nbn' 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.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
MAPKAP1 p.Asp178His 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-ala229asp (accessed [today's date]).

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