Is PTDSS2 p.Ser16Phe (c.47C>T) pathogenic?

PTDSS2 p.Ser16Phe (c.47C>T) is classified Uncertain significance in PTDSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: likely benign (0.1383); Very rare (popmax 0.00985%, nfe).

How common is PTDSS2 p.Ser16Phe (c.47C>T) in the general population?

PTDSS2 p.Ser16Phe (c.47C>T) is very rare (popmax 0.00985%, nfe) (gnomAD).

What do computational predictors say about PTDSS2 p.Ser16Phe (c.47C>T)?

AlphaMissense predicts likely benign (score 0.1383) — an in-silico prediction, not a clinical call.

PTDSS2 p.Ser16Phe

c.47C>T · VCV3784729

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1383 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00985%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1383	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -10.21	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.4	GERP 1, phastCons 0.99
Regional constraint	o/e 0.72	unconstrained · MANE · 38 kb · p 2e-07 · regional, not allelic
Overall
CADD	24.5	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 0.00985% European (non-Finnish) · 97/984,692 alleles

Filtering AF 0.00826% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00759%

Overall 0.00808% 100/1,237,904 alleles · very rare exomes 99/1,085,790 · genomes 1/152,114 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00985%	10,151
Remaining individualsnot grpmax-eligible	0.0066%	15,147

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: PTDSS2
Protein: p.Ser16Phe
Coding: c.47C>T
MANE Select: NM_030783
Type: single nucleotide variant
Location: chr11:450502 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.93 · 1 PDB
Residue 16: the 'disordered' region; a modified residue (phosphoserine)

Full PTDSS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PTDSS2 p.Gln454Arg Uncertain significance ★★ ⚠ same type
PTDSS2 p.Ala199Thr Uncertain significance ★ same type
PTDSS2 p.Ala20Thr Uncertain significance ★ ⚠ same type
PTDSS2 p.Ala20Val Uncertain significance ★ ⚠ same type
PTDSS2 p.Ala37Thr Uncertain significance ★ ⚠ same type
PTDSS2 p.Arg313Ser Uncertain significance ★ ⚠ same type
PTDSS2 p.Arg430His Uncertain significance ★ ⚠ same type
PTDSS2 p.Arg434Trp 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/ptdss2-p-ser16phe (accessed [today's date]).

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