Is CD274 p.Met115Val (c.343A>G) pathogenic?

CD274 p.Met115Val (c.343A>G) is classified Uncertain significance in CD274 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely benign (0.1256); Absent from gnomAD v4.1.

How common is CD274 p.Met115Val (c.343A>G) in the general population?

CD274 p.Met115Val (c.343A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD274 p.Met115Val (c.343A>G)?

AlphaMissense predicts likely benign (score 0.1256) — an in-silico prediction, not a clinical call.

CD274 p.Met115Val

c.343A>G · VCV3998156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1256 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1256	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -4.00	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 0.48	GERP -3.6, phastCons 0.47
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.73 · regional, not allelic
Overall
CADD	12.0	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: CD274
Protein: p.Met115Val
Coding: c.343A>G
MANE Select: NM_014143
Type: single nucleotide variant
Location: chr9:5457369 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 88.13 · 78 PDB
Residue 115: a β-strand; the ig-like v-type domain

Full CD274 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD274 c.*2635A>G Benign ★★ same type
CD274 c.*93G>A Benign ★★ same type
CD274 p.Arg186Ser Uncertain significance ★ ⚠ same type
CD274 p.Asn183Thr Uncertain significance ★ ⚠ same type
CD274 p.Asn278His Uncertain significance ★ ⚠ same type
CD274 p.Glu205Asp Uncertain significance ★ ⚠ same type
CD274 p.Glu217Lys Uncertain significance ★ ⚠ same type
CD274 p.Pro146Thr 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/cd274-p-met115val (accessed [today's date]).

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