Is MAPKAP1 p.Pro247Leu (c.740C>T) pathogenic?

MAPKAP1 p.Pro247Leu (c.740C>T) is classified Uncertain significance in MAPKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely pathogenic (0.9683); Absent from gnomAD v4.1.

How common is MAPKAP1 p.Pro247Leu (c.740C>T) in the general population?

MAPKAP1 p.Pro247Leu (c.740C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPKAP1 p.Pro247Leu (c.740C>T)?

AlphaMissense predicts likely pathogenic (score 0.9683) — an in-silico prediction, not a clinical call.

MAPKAP1 p.Pro247Leu

c.740C>T · rs1830838274 · VCV3123348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9683 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9683	likely pathogenic
REVEL	0.504	indeterminate
SaProt	LLR -14.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 115 kb · p 4.5e-13 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Pro247Leu
Coding: c.740C>T
MANE Select: NM_001006617
dbSNP: rs1830838274
Type: single nucleotide variant
Location: chr9:125559741 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.55 · 23 PDB
Residue 247: 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.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-pro247leu (accessed [today's date]).

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