Is CST1 p.Phe106Ser (c.317T>C) pathogenic?

CST1 p.Phe106Ser (c.317T>C) is classified Uncertain significance in CST1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.7158); Very rare (popmax 0.00133%, afr).

How common is CST1 p.Phe106Ser (c.317T>C) in the general population?

CST1 p.Phe106Ser (c.317T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CST1 p.Phe106Ser (c.317T>C)?

AlphaMissense predicts likely pathogenic (score 0.7158) — an in-silico prediction, not a clinical call.

CST1 p.Phe106Ser

c.317T>C · rs762843755 · VCV2547293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7158 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7158	likely pathogenic · top 8% in CST1
REVEL	0.087	moderately benign-leaning
SaProt	LLR -12.77	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 4.9	GERP 1.2, phastCons 0.24
Regional constraint	o/e 1.39	unconstrained · MANE · 3,047 bp · p 2.5e-07 · regional, not allelic
Overall
CADD	24.1	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 0.00133% African / African-American · 1/74,910 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,036 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,910
European (non-Finnish)	0.000254%	393,345

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.Phe106Ser
Coding: c.317T>C
MANE Select: NM_001898
dbSNP: rs762843755
Type: single nucleotide variant
Location: chr20:23749041 (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.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
CST1 p.Gln98Glu 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-phe106ser (accessed [today's date]).

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