Is MPG p.Arg271His (c.812G>A) pathogenic?

MPG p.Arg271His (c.812G>A) is classified Uncertain significance in MPG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.6275); Very rare (popmax 0.00775%, amr).

How common is MPG p.Arg271His (c.812G>A) in the general population?

MPG p.Arg271His (c.812G>A) is very rare (popmax 0.00775%, amr) (gnomAD).

What do computational predictors say about MPG p.Arg271His (c.812G>A)?

AlphaMissense predicts likely pathogenic (score 0.6275) — an in-silico prediction, not a clinical call.

MPG p.Arg271His

c.812G>A · rs149318391 · VCV2375288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6275 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00775%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6275	likely pathogenic
REVEL	0.73	pathogenic-leaning
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 7,464 bp · p 0.053 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R276H vs ClinVar R271H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00775% Admixed American · 4/51,612 alleles

Filtering AF 0.00261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00152%

Overall 0.000975% 15/1,539,194 alleles · very rare exomes 8/1,386,862 · genomes 7/152,332 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00775%	12,903
African / African-American	0.00274%	36,540
East Asian	0.00227%	44,064
European (non-Finnish)	0.000702%	142,486

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: MPG
Protein: p.Arg271His
Coding: c.812G>A
MANE Select: NM_001015052
dbSNP: rs149318391
Type: single nucleotide variant
Location: chr16:85707 (GRCh38)
Gene constraint: LOEUF 1.468 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.08 · 9 PDB
Residue 276 UniProt numbering: a β-strand

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

Similar variants

MPG p.Val280Ile Uncertain significance ★★ ⚠ same type
MPG p.Ala200Thr Uncertain significance ★ ⚠ same type
MPG p.Ala21Pro Uncertain significance ★ ⚠ same type
MPG p.Ala221Ser Uncertain significance ★ ⚠ same type
MPG p.Ala255Val Uncertain significance ★ ⚠ same type
MPG p.Ala96Glu Uncertain significance ★ ⚠ same type
MPG p.Arg104Gln Uncertain significance ★ ⚠ same type
MPG p.Arg105Gln 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/mpg-p-arg271his (accessed [today's date]).

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