Is CASP7 p.Cys171Ser (c.512G>C) pathogenic?

CASP7 p.Cys171Ser (c.512G>C) is classified Uncertain significance in CASP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely pathogenic (0.954); Rare (popmax 0.134%, mid).

How common is CASP7 p.Cys171Ser (c.512G>C) in the general population?

CASP7 p.Cys171Ser (c.512G>C) is rare (popmax 0.134%, mid) (gnomAD).

What do computational predictors say about CASP7 p.Cys171Ser (c.512G>C)?

AlphaMissense predicts likely pathogenic (score 0.954) — an in-silico prediction, not a clinical call.

CASP7 p.Cys171Ser

c.512G>C · rs201040237 · VCV2357284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.954 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.134%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.954	likely pathogenic
REVEL	0.733	pathogenic-leaning
SaProt	LLR -12.67	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.049 · regional, not allelic
Overall
CADD	28.2	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 0.134% Middle Eastern · 8/5,956 alleles

Filtering AF 0.0668% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0488%

Overall 0.0137% 218/1,593,516 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.134%	745
Ashkenazi Jewishnot grpmax-eligible	0.0315%	3,170
Remaining individualsnot grpmax-eligible	0.026%	3,840
South Asian	0.0239%	4,192
European (non-Finnish)	0.0137%	7,284
Admixed American	0.00554%	18,063

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: CASP7
Protein: p.Cys171Ser
Coding: c.512G>C
MANE Select: NM_001227
dbSNP: rs201040237
Type: single nucleotide variant
Location: chr10:113725497 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.05 · 47 PDB

Full CASP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASP7 p.Asp255Glu Benign ★★ same type
CASP7 p.Ala164Val Uncertain significance ★ ⚠ same type
CASP7 p.Ala270Ser Uncertain significance ★ ⚠ same type
CASP7 p.Ala270Val Uncertain significance ★ ⚠ same type
CASP7 p.Arg210Gln Uncertain significance ★ ⚠ same type
CASP7 p.Arg28Gln Uncertain significance ★ ⚠ same type
CASP7 p.Arg52Gln Uncertain significance ★ ⚠ same type
CASP7 p.Asn61Lys 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/casp7-p-cys171ser (accessed [today's date]).

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