Is MAPKAP1 p.Arg15Gln (c.44G>A) pathogenic?

MAPKAP1 p.Arg15Gln (c.44G>A) is classified Uncertain significance in MAPKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-05). AlphaMissense: likely pathogenic (0.8453); Rare (popmax 0.141%, afr).

How common is MAPKAP1 p.Arg15Gln (c.44G>A) in the general population?

MAPKAP1 p.Arg15Gln (c.44G>A) is rare (popmax 0.141%, afr) (gnomAD).

What do computational predictors say about MAPKAP1 p.Arg15Gln (c.44G>A)?

AlphaMissense predicts likely pathogenic (score 0.8453) — an in-silico prediction, not a clinical call.

MAPKAP1 p.Arg15Gln

c.44G>A · rs144290254 · VCV2406938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8453 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.141%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8453	likely pathogenic
REVEL	0.445	indeterminate
SaProt	LLR -7.46	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 5.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 83 bp · p 0.00033 · regional, not allelic
Overall
CADD	28.7	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 0.141% African / African-American · 106/75,004 alleles

Filtering AF 0.119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.00694% 112/1,614,106 alleles · rare exomes 61/1,461,876 · genomes 51/152,230 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.141%	708
Admixed American	0.00666%	15,006
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	8.47e-05%	1,180,008

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.Arg15Gln
Coding: c.44G>A
MANE Select: NM_001006617
dbSNP: rs144290254
Type: single nucleotide variant
Location: chr9:125672531 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.55 · 23 PDB
Residue 15: an α-helix; 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.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-arg15gln (accessed [today's date]).

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