Is MAPKAP1 p.Val475Ile (c.1423G>A) pathogenic?

MAPKAP1 p.Val475Ile (c.1423G>A) is classified Uncertain significance in MAPKAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). AlphaMissense: likely benign (0.133); Ultra-rare (popmax 0.0319%, sas).

How common is MAPKAP1 p.Val475Ile (c.1423G>A) in the general population?

MAPKAP1 p.Val475Ile (c.1423G>A) is ultra-rare (popmax 0.0319%, sas) (gnomAD).

What do computational predictors say about MAPKAP1 p.Val475Ile (c.1423G>A)?

AlphaMissense predicts likely benign (score 0.133) — an in-silico prediction, not a clinical call.

MAPKAP1 p.Val475Ile

c.1423G>A · VCV4051667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.133 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0319%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.133	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -8.91	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 1.4	GERP -2.1, phastCons 0.77
Regional constraint	o/e 0.69	unconstrained · MANE · 104 kb · p 3.8e-07 · regional, not allelic
Overall
CADD	19.1	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 0.0319% South Asian · 29/91,012 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00645% 104/1,613,330 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0319%	3,138
African / African-American	0.016%	6,253
East Asian	0.00669%	14,957
Remaining individualsnot grpmax-eligible	0.0048%	20,825
European (non-Finnish)	0.00475%	21,061
Admixed American	0.00167%	59,892

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.Val475Ile
Coding: c.1423G>A
MANE Select: NM_001006617
Type: single nucleotide variant
Location: chr9:125444521 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.55 · 23 PDB
Residue 475: the sin1-type ph domain; an α-helix; the 'interaction with atf2' 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-val475ile (accessed [today's date]).

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