Is PPAT p.Met293Ile (c.879G>A) pathogenic?

PPAT p.Met293Ile (c.879G>A) is classified Likely benign in PPAT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-28). AlphaMissense: likely benign (0.1266); Rare (popmax 0.113%, mid).

How common is PPAT p.Met293Ile (c.879G>A) in the general population?

PPAT p.Met293Ile (c.879G>A) is rare (popmax 0.113%, mid) (gnomAD).

What do computational predictors say about PPAT p.Met293Ile (c.879G>A)?

AlphaMissense predicts likely benign (score 0.1266) — an in-silico prediction, not a clinical call.

PPAT p.Met293Ile

c.879G>A · rs201692437 · VCV2393357

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1266 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.113%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1266	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -3.96	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 -0.45	GERP -1.8, phastCons 0.1
Overall
CADD	7.651	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 0.113% Middle Eastern · 5/4,430 alleles

Filtering AF 0.0444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0288%

Overall 0.0142% 224/1,575,512 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.113%	886
Remaining individualsnot grpmax-eligible	0.0214%	4,669
European (non-Finnish)	0.0173%	5,781
African / African-American	0.0055%	18,197
Admixed American	0.0019%	52,640

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: PPAT
Protein: p.Met293Ile
Coding: c.879G>A
MANE Select: NM_025233 · reported on NM_002703
dbSNP: rs201692437
Type: single nucleotide variant
Location: chr4:56401337 (GRCh38)
Structure: AlphaFold pLDDT 89.51
Residue 293: a UniProt-annotated variant site (in nbia6; reduced protein abundance); the 'phosphopantetheine adenylyltransferase domain' region

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

Similar variants

COASY p.Arg293Leu Uncertain significance ★★ ⚠ same residue
COASY c.1486-3C>G Pathogenic/Likely pathogenic ★★ same type
COASY p.Ala214Val Likely pathogenic ★★ ⚠ same type
COASY p.Arg377Ter Pathogenic/Likely pathogenic ★★ same type
COASY p.Arg499Cys Pathogenic ★★ same type
COASY p.Gln523Ter Pathogenic ★★ same type
COASY p.Ala206Ser Uncertain significance ★★ ⚠ same type
COASY p.Ala311Val 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/ppat-p-met293ile (accessed [today's date]).

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