Is CST5 p.Asn101Ser (c.302A>G) pathogenic?

CST5 p.Asn101Ser (c.302A>G) is classified Uncertain significance in CST5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely benign (0.1016); Ultra-rare (popmax 0.0231%, nfe).

How common is CST5 p.Asn101Ser (c.302A>G) in the general population?

CST5 p.Asn101Ser (c.302A>G) is ultra-rare (popmax 0.0231%, nfe) (gnomAD).

What do computational predictors say about CST5 p.Asn101Ser (c.302A>G)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

CST5 p.Asn101Ser

c.302A>G · VCV3497970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -8.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP -0.87
Regional constraint	o/e 1.25	unconstrained · MANE · 3,485 bp · p 0.00076 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% European (non-Finnish) · 272/1,179,952 alleles

Filtering AF 0.0208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0199%

Overall 0.0175% 282/1,613,960 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0231%	4,338
Middle Eastern	0.0164%	6,084
Finnishnot grpmax-eligible	0.00469%	21,339
Admixed American	0.00333%	30,005
Remaining individualsnot grpmax-eligible	0.0032%	31,240
East Asian	0.00223%	44,886
African / African-American	0.00133%	74,938

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: CST5
Protein: p.Asn101Ser
Coding: c.302A>G
MANE Select: NM_001900
Type: single nucleotide variant
Location: chr20:23877548 (GRCh38)
Gene constraint: LOEUF 1.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.46 · 2 PDB
Residue 101: a disulfide bond

Full CST5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST5 p.Ala23Thr Uncertain significance ★ ⚠ same type
CST5 p.Ala31Thr Uncertain significance ★ ⚠ same type
CST5 p.Ala36Val Uncertain significance ★ ⚠ same type
CST5 p.Ala51Val Uncertain significance ★ ⚠ same type
CST5 p.Arg140Trp Uncertain significance ★ ⚠ same type
CST5 p.Asn83His Uncertain significance ★ ⚠ same type
CST5 p.Asp41Gly Uncertain significance ★ ⚠ same type
CST5 p.Cys46Phe 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/cst5-p-asn101ser (accessed [today's date]).

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