Is CST2 p.Tyr83Ser (c.248A>C) pathogenic?

CST2 p.Tyr83Ser (c.248A>C) is classified Uncertain significance in CST2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). AlphaMissense: likely pathogenic (0.5847); Absent from gnomAD v4.1.

How common is CST2 p.Tyr83Ser (c.248A>C) in the general population?

CST2 p.Tyr83Ser (c.248A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CST2 p.Tyr83Ser (c.248A>C)?

AlphaMissense predicts likely pathogenic (score 0.5847) — an in-silico prediction, not a clinical call.

CST2 p.Tyr83Ser

c.248A>C · rs2514849272 · VCV3078402

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5847 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5847	likely pathogenic · top 10% in CST2
REVEL	0.222	benign-leaning
SaProt	LLR -13.10	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.63	GERP 1.4, phastCons 0.32
Regional constraint	o/e 1.40	unconstrained · MANE · 2,637 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	20.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CST2
Protein: p.Tyr83Ser
Coding: c.248A>C
MANE Select: NM_001322
dbSNP: rs2514849272
Type: single nucleotide variant
Location: chr20:23825304 (GRCh38)
Gene constraint: LOEUF 1.951 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.89

Full CST2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST2 p.Arg69Trp Benign ★★ ⚠ same type
CST2 p.Ala16Val Uncertain significance ★ ⚠ same type
CST2 p.Ala2Val Uncertain significance ★ ⚠ same type
CST2 p.Ala58Val Uncertain significance ★ ⚠ same type
CST2 p.Ala73Val Uncertain significance ★ ⚠ same type
CST2 p.Arg130Gly Uncertain significance ★ ⚠ same type
CST2 p.Arg28Lys Uncertain significance ★ ⚠ same type
CST2 p.Arg46His 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/cst2-p-tyr83ser (accessed [today's date]).

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