Is PTGDR p.Ser352Phe (c.1055C>T) pathogenic?

PTGDR p.Ser352Phe (c.1055C>T) is classified Uncertain significance in PTGDR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.1377); Ultra-rare (popmax 0.0998%, sas).

How common is PTGDR p.Ser352Phe (c.1055C>T) in the general population?

PTGDR p.Ser352Phe (c.1055C>T) is ultra-rare (popmax 0.0998%, sas) (gnomAD).

What do computational predictors say about PTGDR p.Ser352Phe (c.1055C>T)?

AlphaMissense predicts likely benign (score 0.1377) — an in-silico prediction, not a clinical call.

PTGDR p.Ser352Phe

c.1055C>T · rs201662277 · VCV2205769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1377 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0998%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1377	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -8.20	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 0.44	GERP -2.5, phastCons 0.04
Regional constraint	o/e 1.09	unconstrained · MANE · 7,146 bp · p 0.045 · regional, not allelic
Overall
CADD	14.43	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 0.0998% South Asian · 90/90,190 alleles

Filtering AF 0.0831% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0769%

Overall 0.00826% 131/1,586,022 alleles · ultra-rare exomes 123/1,434,086 · genomes 8/151,936 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0998%	1,002
Admixed American	0.0201%	4,970
Remaining individualsnot grpmax-eligible	0.00325%	30,756
European (non-Finnish)	0.00225%	44,446
African / African-American	0.00135%	74,236

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: PTGDR
Protein: p.Ser352Phe
Coding: c.1055C>T
MANE Select: NM_000953
dbSNP: rs201662277
Type: single nucleotide variant
Location: chr14:52274939 (GRCh38)
Gene constraint: LOEUF 1.523 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.06 · 8 PDB

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

Similar variants

PTGDR p.Arg7Cys Benign ★★ same type
PTGDR p.Ala107Asp Uncertain significance ★ ⚠ same type
PTGDR p.Ala162Thr Uncertain significance ★ ⚠ same type
PTGDR p.Ala20Val Uncertain significance ★ ⚠ same type
PTGDR p.Ala248Val Uncertain significance ★ ⚠ same type
PTGDR p.Ala268Glu Uncertain significance ★ ⚠ same type
PTGDR p.Ala99Ser Uncertain significance ★ ⚠ same type
PTGDR p.Arg223Gly 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/ptgdr-p-ser352phe (accessed [today's date]).

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