Is CSTPP1 p.Ser313Leu (c.938C>T) pathogenic?

CSTPP1 p.Ser313Leu (c.938C>T) is classified Uncertain significance in CSTPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). Very rare (popmax 0.00334%, amr).

How common is CSTPP1 p.Ser313Leu (c.938C>T) in the general population?

CSTPP1 p.Ser313Leu (c.938C>T) is very rare (popmax 0.00334%, amr) (gnomAD).

CSTPP1 p.Ser313Leu

c.938C>T · rs376947288 · VCV3078471

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.046	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -1.4
Overall
CADD	7.103	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,968 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00415% 67/1,613,684 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0453%	2,207
Admixed Americangrpmax	0.00334%	29,984
European (non-Finnish)	0.0028%	35,753
East Asian	0.00223%	44,886
Remaining individualsnot grpmax-eligible	0.0016%	62,462
South Asian	0.0011%	91,050

Finnish 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: CSTPP1
Protein: p.Ser313Leu
Coding: c.938C>T
MANE Select: NM_024113 · reported on NM_001003678
dbSNP: rs376947288
Type: single nucleotide variant
Location: chr11:47164209 (GRCh38)
Structure: AlphaFold pLDDT 81.05
Residue 313: the 'required for interaction with tpgs2' region; the 'disordered' region

Full CSTPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSTPP1 p.Arg18Gln Uncertain significance ★ ⚠ same type
CSTPP1 p.Asn92Lys Uncertain significance ★ ⚠ same type
CSTPP1 p.Asp260His Uncertain significance ★ ⚠ same type
CSTPP1 p.Glu328Lys Uncertain significance ★ ⚠ same type
CSTPP1 p.Pro218Ser Uncertain significance ★ ⚠ same type
CSTPP1 p.Asp327= Likely benign ★ 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/cstpp1-p-ser313leu (accessed [today's date]).

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