Is PPAT p.Arg210Cys (c.628C>T) pathogenic?

PPAT p.Arg210Cys (c.628C>T) is classified Uncertain significance in PPAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.1699); Very rare (popmax 0.00402%, afr).

How common is PPAT p.Arg210Cys (c.628C>T) in the general population?

PPAT p.Arg210Cys (c.628C>T) is very rare (popmax 0.00402%, afr) (gnomAD).

What do computational predictors say about PPAT p.Arg210Cys (c.628C>T)?

AlphaMissense predicts likely benign (score 0.1699) — an in-silico prediction, not a clinical call.

PPAT p.Arg210Cys

c.628C>T · VCV3782164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1699 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00402%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1699	likely benign
REVEL	0.657	pathogenic-leaning
SaProt	LLR -9.99	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Overall
CADD	28.6	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 0.00402% African / African-American · 3/74,686 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00118% 19/1,610,704 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00402%	24,895
European (non-Finnish)	0.00136%	73,658

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.Arg210Cys
Coding: c.628C>T
MANE Select: NM_025233 · reported on NM_002703
Type: single nucleotide variant
Location: chr4:56403073 (GRCh38)
Structure: AlphaFold pLDDT 89.51
Residue 210: 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

PPAT p.Arg210His 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-arg210cys (accessed [today's date]).

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