Is PTDSS2 p.Asp435= (c.1305C>T) pathogenic?

PTDSS2 p.Asp435= (c.1305C>T) is classified Likely benign in PTDSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). Low-frequency (popmax 1.27%, mid).

How common is PTDSS2 p.Asp435= (c.1305C>T) in the general population?

PTDSS2 p.Asp435= (c.1305C>T) is low-frequency (popmax 1.27%, mid) (gnomAD).

PTDSS2 p.Asp435=

c.1305C>T · VCV4280768

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.27%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP -0.13, phastCons 1
Overall
CADD	6.601	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.27% Middle Eastern · 77/6,062 alleles

Filtering AF 1.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.958%

Overall 0.523% 8,432/1,613,240 alleles · low-frequency exomes 7,825/1,460,928 · genomes 607/152,312 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.61%	62
Middle Easterngrpmax	1.27%	79
South Asian	0.667%	150
Remaining individualsnot grpmax-eligible	0.597%	168
European (non-Finnish)	0.561%	178
Admixed American	0.295%	339
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0933%	1,072
Finnishnot grpmax-eligible	0.0411%	2,430

Ashkenazi Jewish 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: PTDSS2
Protein: p.Asp435=
Coding: c.1305C>T
MANE Select: NM_030783
Type: single nucleotide variant
Location: chr11:490423 (GRCh38)
Gene constraint: LOEUF 0.802 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.93 · 1 PDB
Residue 435: an α-helix

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-asp435 (accessed [today's date]).

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