Is CST1 p.Val87Ala (c.260T>C) pathogenic?

CST1 p.Val87Ala (c.260T>C) is classified Uncertain significance in CST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: ambiguous (0.3483); Ultra-rare (popmax 0.0164%, mid).

How common is CST1 p.Val87Ala (c.260T>C) in the general population?

CST1 p.Val87Ala (c.260T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CST1 p.Val87Ala (c.260T>C)?

AlphaMissense predicts ambiguous (score 0.3483) — an in-silico prediction, not a clinical call.

CST1 p.Val87Ala

c.260T>C · VCV3497952

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3483 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3483	ambiguous
REVEL	0.146	moderately benign-leaning
SaProt	LLR -10.94	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 0.3, phastCons 0.3
Regional constraint	o/e 1.39	unconstrained · MANE · 3,047 bp · p 2.5e-07 · regional, not allelic
Overall
CADD	19.71	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,613,966 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
East Asian	0.00223%	44,876
European (non-Finnish)	0.000169%	590,009

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: CST1
Protein: p.Val87Ala
Coding: c.260T>C
MANE Select: NM_001898
Type: single nucleotide variant
Location: chr20:23749098 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.69

Full CST1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST1 p.Val87Ile Uncertain significance ★ ⚠ same residue
CST1 p.Ala18Thr Uncertain significance ★ ⚠ same type
CST1 p.Ala51Thr Uncertain significance ★ ⚠ same type
CST1 p.Ala73Thr Uncertain significance ★ ⚠ same type
CST1 p.Arg131Ser Uncertain significance ★ ⚠ same type
CST1 p.Arg69Trp Uncertain significance ★ ⚠ same type
CST1 p.Arg72Thr Uncertain significance ★ ⚠ same type
CST1 p.Asp61Val 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/cst1-p-val87ala (accessed [today's date]).

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