Is PTGES p.Val29Ala (c.86T>C) pathogenic?

PTGES p.Val29Ala (c.86T>C) is classified Uncertain significance in PTGES (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: likely benign (0.0863); Ultra-rare (popmax 0.0217%, nfe).

How common is PTGES p.Val29Ala (c.86T>C) in the general population?

PTGES p.Val29Ala (c.86T>C) is ultra-rare (popmax 0.0217%, nfe) (gnomAD).

What do computational predictors say about PTGES p.Val29Ala (c.86T>C)?

AlphaMissense predicts likely benign (score 0.0863) — an in-silico prediction, not a clinical call.

PTGES p.Val29Ala

c.86T>C · rs199664006 · VCV2352715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0863 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0863	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.52	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 -0.036	GERP -3.2, phastCons 0.003
Regional constraint	o/e 0.85	unconstrained · MANE · 13 kb · p 0.024 · regional, not allelic
Overall
CADD	13.0	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

Grpmax group 0.0217% European (non-Finnish) · 256/1,180,056 alleles

Filtering AF 0.0195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0186%

Overall 0.0165% 267/1,613,644 alleles · ultra-rare exomes 254/1,461,406 · genomes 13/152,238 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0217%	4,610
Remaining individualsnot grpmax-eligible	0.0096%	10,414
African / African-American	0.004%	24,979
Admixed American	0.00333%	30,007

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: PTGES
Protein: p.Val29Ala
Coding: c.86T>C
MANE Select: NM_004878
dbSNP: rs199664006
Type: single nucleotide variant
Location: chr9:129752927 (GRCh38)
Gene constraint: LOEUF 0.963 · pLI 0.40 (gnomAD)
Structure: AlphaFold pLDDT 96.25 · 18 PDB
Residue 29: an α-helix

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

Similar variants

PTGES p.Arg60= Benign ★★ same type
PTGES p.Ser61= Benign ★★ same type
PTGES p.Val7Glu Benign ★★ same type
PTGES p.Ala149Thr Uncertain significance ★ ⚠ same type
PTGES p.Arg67Cys Uncertain significance ★ ⚠ same type
PTGES p.Glu147Asp Uncertain significance ★ ⚠ same type
PTGES p.Gly93Ser Uncertain significance ★ ⚠ same type
PTGES p.His102Tyr 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/ptges-p-val29ala (accessed [today's date]).

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