Is MAPK7 p.Pro551Ser (c.1651C>T) pathogenic?

MAPK7 p.Pro551Ser (c.1651C>T) is classified Benign/Likely benign in MAPK7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-18). AlphaMissense: likely benign (0.0742); Low-frequency (popmax 2.82%, afr).

How common is MAPK7 p.Pro551Ser (c.1651C>T) in the general population?

MAPK7 p.Pro551Ser (c.1651C>T) is low-frequency (popmax 2.82%, afr) (gnomAD).

What do computational predictors say about MAPK7 p.Pro551Ser (c.1651C>T)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

MAPK7 p.Pro551Ser

c.1651C>T · rs144954037 · VCV777151

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.82%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -6.32	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 2.7	phastCons 0.99
Regional constraint	o/e 0.80	unconstrained · MANE · 1,234 bp · p 6.6e-06 · regional, not allelic
Overall
CADD	20.2	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 2.82% African / African-American · 2,062/73,122 alleles

Filtering AF 2.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.68%

Overall 0.164% 2,546/1,551,746 alleles · low-frequency exomes 1,274/1,399,518 · genomes 1,272/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.82%	35
Remaining individualsnot grpmax-eligible	0.251%	398
Admixed American	0.249%	402
Middle Eastern	0.234%	427
Ashkenazi Jewishnot grpmax-eligible	0.119%	842
Finnishnot grpmax-eligible	0.0134%	7,458
European (non-Finnish)	0.0123%	8,136
South Asian	0.0107%	9,352

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: MAPK7
Protein: p.Pro551Ser
Coding: c.1651C>T
MANE Select: NM_002749
dbSNP: rs144954037
Type: single nucleotide variant
Location: chr17:19381954 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 14 PDB
Residue 551: the 'disordered' region; the 'may not be required for kinase activity; required to stimulate mef2c activity' region

Full MAPK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK7 p.Ala288Ser Uncertain significance ★ ⚠ same type
MAPK7 p.Ala29Gly Uncertain significance ★ ⚠ same type
MAPK7 p.Ala334Thr Uncertain significance ★ ⚠ same type
MAPK7 p.Ala348Ser Uncertain significance ★ ⚠ same type
MAPK7 p.Ala360Val Uncertain significance ★ ⚠ same type
MAPK7 p.Ala481Ser Uncertain significance ★ ⚠ same type
MAPK7 p.Ala497Val Uncertain significance ★ ⚠ same type
MAPK7 p.Ala501Val 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/mapk7-p-pro551ser (accessed [today's date]).

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