Is CST3 p.Arg79Ser (c.235C>A) pathogenic?

CST3 p.Arg79Ser (c.235C>A) is classified Benign/Likely benign in CST3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-18). AlphaMissense: ambiguous (0.5171); Rare (popmax 0.291%, eas).

How common is CST3 p.Arg79Ser (c.235C>A) in the general population?

CST3 p.Arg79Ser (c.235C>A) is rare (popmax 0.291%, eas) (gnomAD).

What do computational predictors say about CST3 p.Arg79Ser (c.235C>A)?

AlphaMissense predicts ambiguous (score 0.5171) — an in-silico prediction, not a clinical call.

CST3 p.Arg79Ser

c.235C>A · rs574152075 · VCV719121

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5171 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.291%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5171	ambiguous
REVEL	0.062	moderately benign-leaning
SaProt	LLR -8.46	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.78	GERP 0.49
Regional constraint	o/e 1.16	unconstrained · MANE · 3,943 bp · p 0.022 · regional, not allelic
Overall
CADD	22.8	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 0.291% East Asian · 108/37,150 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.23%

Overall 0.0101% 154/1,519,716 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.291%	344
Remaining individualsnot grpmax-eligible	0.0665%	1,503
Admixed American	0.00418%	23,906
African / African-American	0.00288%	34,694
South Asian	0.00124%	80,846
European (non-Finnish)	0.000176%	567,324

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: CST3
Protein: p.Arg79Ser
Coding: c.235C>A
MANE Select: NM_000099
dbSNP: rs574152075
Type: single nucleotide variant
Location: chr20:23637628 (GRCh38)
Gene constraint: LOEUF 1.912 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.56 · 11 PDB
Residue 79: a β-strand

Full CST3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST3 p.Arg71His Uncertain significance ★★ ⚠ same type
CST3 p.His112Arg Uncertain significance ★★ ⚠ same type
CST3 p.Met67Val Uncertain significance ★★ ⚠ same type
CST3 p.Pro8Ser Uncertain significance ★★ ⚠ same type
CST3 c.243+11C>T Likely benign ★★ same type
CST3 p.Ala25Thr Benign/Likely benign ★★ same type
CST3 p.Ala72Ser Benign ★★ ⚠ same type
CST3 p.Arg6= Benign/Likely benign ★★ 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/cst3-p-arg79ser (accessed [today's date]).

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