Is MPEG1 p.Arg149Gln (c.446G>A) pathogenic?

MPEG1 p.Arg149Gln (c.446G>A) is classified Uncertain significance in MPEG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.0899); Very rare (popmax 0.00334%, sas).

How common is MPEG1 p.Arg149Gln (c.446G>A) in the general population?

MPEG1 p.Arg149Gln (c.446G>A) is very rare (popmax 0.00334%, sas) (gnomAD).

What do computational predictors say about MPEG1 p.Arg149Gln (c.446G>A)?

AlphaMissense predicts likely benign (score 0.0899) — an in-silico prediction, not a clinical call.

MPEG1 p.Arg149Gln

c.446G>A · VCV4109765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0899 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0899	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -13.34	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 3.4	GERP 0.47, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 2,147 bp · p 0.89 · regional, not allelic
Overall
CADD	22.3	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 0.00334% South Asian · 3/89,796 alleles

Filtering AF 0.000887% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000446%

Overall 0.00106% 17/1,601,338 alleles · very rare exomes 17/1,458,484 · genomes 0/142,854 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00334%	29,932
East Asian	0.00226%	44,324
African / African-American	0.00139%	71,944
European (non-Finnish)	0.00102%	97,852

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.Arg149Gln
Coding: c.446G>A
MANE Select: NM_001039396
Type: single nucleotide variant
Location: chr11:59212420 (GRCh38)
Gene constraint: LOEUF 1.941 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 83.22 · 5 PDB
Residue 149: a β-strand; the macpf domain

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

Similar variants

MPEG1 p.Arg149Ter Uncertain significance same residue
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

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-arg149gln (accessed [today's date]).

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