Is MPEG1 p.Arg55Gln (c.164G>A) pathogenic?

MPEG1 p.Arg55Gln (c.164G>A) is classified Uncertain significance in MPEG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.1275); Ultra-rare (popmax 0.0383%, amr).

How common is MPEG1 p.Arg55Gln (c.164G>A) in the general population?

MPEG1 p.Arg55Gln (c.164G>A) is ultra-rare (popmax 0.0383%, amr) (gnomAD).

What do computational predictors say about MPEG1 p.Arg55Gln (c.164G>A)?

AlphaMissense predicts likely benign (score 0.1275) — an in-silico prediction, not a clinical call.

MPEG1 p.Arg55Gln

c.164G>A · rs775131648 · VCV2388742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1275 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1275	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -10.71	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,147 bp · p 0.89 · regional, not allelic
Overall
CADD	25.5	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 0.0383% Admixed American · 23/60,010 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.0039% 63/1,614,090 alleles · ultra-rare exomes 51/1,461,894 · genomes 12/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0383%	2,609
African / African-American	0.0187%	5,352
East Asian	0.00445%	22,449
South Asian	0.00439%	22,773
Finnishnot grpmax-eligible	0.00312%	32,021
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.00144%	69,414

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: MPEG1
Protein: p.Arg55Gln
Coding: c.164G>A
MANE Select: NM_001039396
dbSNP: rs775131648
Type: single nucleotide variant
Location: chr11:59212702 (GRCh38)
Gene constraint: LOEUF 1.941 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 83.22 · 5 PDB
Residue 55: a turn; the macpf domain

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-arg55gln (accessed [today's date]).

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