Is MPEG1 p.Pro552Gln (c.1655C>A) pathogenic?

MPEG1 p.Pro552Gln (c.1655C>A) is classified Uncertain significance in MPEG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-09). AlphaMissense: likely benign (0.094); Absent from gnomAD v4.1.

How common is MPEG1 p.Pro552Gln (c.1655C>A) in the general population?

MPEG1 p.Pro552Gln (c.1655C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MPEG1 p.Pro552Gln (c.1655C>A)?

AlphaMissense predicts likely benign (score 0.094) — an in-silico prediction, not a clinical call.

MPEG1 p.Pro552Gln

c.1655C>A · rs7926933 · VCV3201660

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.094 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.094	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -3.16	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 6.9	GERP 0.67, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,147 bp · p 0.89 · regional, not allelic
Overall
CADD	18.71	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

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: MPEG1
Protein: p.Pro552Gln
Coding: c.1655C>A
MANE Select: NM_001039396
dbSNP: rs7926933
Type: single nucleotide variant
Location: chr11:59211211 (GRCh38)
Gene constraint: LOEUF 1.941 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 83.22 · 5 PDB
Residue 552: a UniProt-annotated variant site (in imd77; decreased defense response to bacterium); a UniProt-annotated variant site (in); the 'p2' region

Full MPEG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MPEG1 p.Ala525Val Uncertain significance ★★ ⚠ same type
MPEG1 p.Gln259Glu Uncertain significance ★★ ⚠ same type
MPEG1 p.Gln713Arg Uncertain significance ★★ ⚠ same type
MPEG1 p.His420Tyr Uncertain significance ★★ ⚠ same type
MPEG1 p.Ala467= Benign ★★ same type
MPEG1 p.Thr73Ala Likely benign ★★ same type
MPEG1 p.Ala238Thr Uncertain significance ★ ⚠ same type
MPEG1 p.Ala238Val 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/mpeg1-p-pro552gln (accessed [today's date]).

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