Is CST5 p.Val58Ile (c.172G>A) pathogenic?

CST5 p.Val58Ile (c.172G>A) is classified Uncertain significance in CST5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: likely benign (0.1111); Very rare (popmax 0.00223%, eas).

How common is CST5 p.Val58Ile (c.172G>A) in the general population?

CST5 p.Val58Ile (c.172G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CST5 p.Val58Ile (c.172G>A)?

AlphaMissense predicts likely benign (score 0.1111) — an in-silico prediction, not a clinical call.

CST5 p.Val58Ile

c.172G>A · rs751792054 · VCV2623691

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1111 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1111	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.28	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 -4.4	GERP -0.84
Regional constraint	o/e 1.25	unconstrained · MANE · 3,485 bp · p 0.00076 · regional, not allelic
Overall
CADD	7.832	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 0.00223% East Asian · 1/44,870 alleles

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

Overall 0.000342% 5/1,461,832 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,870
Admixed American	0.00167%	60,016
European (non-Finnish)	0.000254%	393,326

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.Val58Ile
Coding: c.172G>A
MANE Select: NM_001900
dbSNP: rs751792054
Type: single nucleotide variant
Location: chr20:23879505 (GRCh38)
Gene constraint: LOEUF 1.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.46 · 2 PDB
Residue 58: an α-helix

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.Asn101Ser Uncertain significance ★ ⚠ same type
CST5 p.Asn83His Uncertain significance ★ ⚠ same type
CST5 p.Asp41Gly 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-val58ile (accessed [today's date]).

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