Is CST7 p.Arg106Ser (c.316C>A) pathogenic?

CST7 p.Arg106Ser (c.316C>A) is classified Likely benign in CST7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.0823); Very rare (popmax 0.00223%, eas).

How common is CST7 p.Arg106Ser (c.316C>A) in the general population?

CST7 p.Arg106Ser (c.316C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CST7 p.Arg106Ser (c.316C>A)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

CST7 p.Arg106Ser

c.316C>A · rs371415469 · VCV3078419

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · 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	0.0823	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -5.21	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 -0.17	GERP -3.5
Regional constraint	o/e 1.08	unconstrained · MANE · 10 kb · p 0.29 · regional, not allelic
Overall
CADD	0.003	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 0.00223% East Asian · 1/44,882 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000684% 10/1,461,706 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
South Asian	0.0022%	45,542
European (non-Finnish)	0.000593%	168,558

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: CST7
Protein: p.Arg106Ser
Coding: c.316C>A
MANE Select: NM_003650
dbSNP: rs371415469
Type: single nucleotide variant
Location: chr20:24959000 (GRCh38)
Gene constraint: LOEUF 1.742 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.78 · 1 PDB
Residue 106: a disulfide bond

Full CST7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CST7 p.Ala9Val Uncertain significance ★ ⚠ same type
CST7 p.Arg33His Uncertain significance ★ ⚠ same type
CST7 p.Arg96Ser Uncertain significance ★ ⚠ same type
CST7 p.Asn61His Uncertain significance ★ ⚠ same type
CST7 p.Cys63Arg Uncertain significance ★ ⚠ same type
CST7 p.Cys99Ser Uncertain significance ★ ⚠ same type
CST7 p.Glu138Gln Uncertain significance ★ ⚠ same type
CST7 p.Glu138Lys 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/cst7-p-arg106ser (accessed [today's date]).

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