Is CST7 p.Phe70Val (c.208T>G) pathogenic?

CST7 p.Phe70Val (c.208T>G) is classified Uncertain significance in CST7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely pathogenic (0.8711); Very rare (popmax 0.000339%, nfe).

How common is CST7 p.Phe70Val (c.208T>G) in the general population?

CST7 p.Phe70Val (c.208T>G) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CST7 p.Phe70Val (c.208T>G)?

AlphaMissense predicts likely pathogenic (score 0.8711) — an in-silico prediction, not a clinical call.

CST7 p.Phe70Val

c.208T>G · rs2087865903 · VCV2487214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8711 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8711	likely pathogenic · top 6% in CST7
REVEL	0.336	indeterminate
SaProt	LLR -15.64	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.52, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 10 kb · p 0.29 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000339% European (non-Finnish) · 4/1,179,782 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,644 alleles · very rare

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.Phe70Val
Coding: c.208T>G
MANE Select: NM_003650
dbSNP: rs2087865903
Type: single nucleotide variant
Location: chr20:24957424 (GRCh38)
Gene constraint: LOEUF 1.742 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.78 · 1 PDB
Residue 70: a β-strand

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-phe70val (accessed [today's date]).

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