Is PPAT p.Arg351Trp (c.1051C>T) pathogenic?

PPAT p.Arg351Trp (c.1051C>T) is classified Likely benign in PPAT (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.8961); Very rare (popmax 0.000678%, nfe); Associated with EBV-positive nodal T- and NK-cell lymphoma.

What condition is associated with PPAT p.Arg351Trp (c.1051C>T)?

PPAT p.Arg351Trp (c.1051C>T) is associated with EBV-positive nodal T- and NK-cell lymphoma (ClinVar).

How common is PPAT p.Arg351Trp (c.1051C>T) in the general population?

PPAT p.Arg351Trp (c.1051C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about PPAT p.Arg351Trp (c.1051C>T)?

AlphaMissense predicts likely pathogenic (score 0.8961) — an in-silico prediction, not a clinical call.

PPAT p.Arg351Trp

c.1051C>T · rs2545651685 · VCV2681496

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EBV-positive nodal T- and NK-cell lymphoma

Computational evidence

Protein change
AlphaMissense	0.8961	likely pathogenic · top 9% in PPAT
REVEL	0.965	strongly pathogenic-leaning
SaProt	LLR -15.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.4	GERP 1.6, phastCons 1
Overall
CADD	33.0	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 0.000678% European (non-Finnish) · 8/1,179,864 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000684% 10/1,461,642 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,251
European (non-Finnish)grpmax	0.000678%	147,483

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg351Trp
Coding: c.1051C>T
MANE Select: NM_025233 · reported on NM_002703
dbSNP: rs2545651685
Type: single nucleotide variant
Location: chr4:56399364 (GRCh38)
Structure: AlphaFold pLDDT 89.51
Residue 351: 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

Disease context

EBV-positive nodal T- and NK-cell lymphoma

Similar variants

COASY c.1486-3C>G Pathogenic/Likely pathogenic ★★ same condition
COASY p.Ala214Val Likely pathogenic ★★ ⚠ same condition
COASY p.Gln523Ter Pathogenic ★★ same condition
COASY p.Lys371Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
COASY p.Ala395= Likely benign same condition
COASY p.Gly432fs Likely pathogenic ★ same condition
COASY p.Ile469Ter Conflicting classifications of pathogenicity ★ same condition
COASY p.Arg377Ter Pathogenic/Likely pathogenic ★★ 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-arg351trp (accessed [today's date]).

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