Is CASP7 p.Asp255Glu (c.765C>G) pathogenic?

CASP7 p.Asp255Glu (c.765C>G) is classified Benign in CASP7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-02-23). AlphaMissense: likely benign (0.0723); Common (popmax 44.3%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CASP7 p.Asp255Glu (c.765C>G)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

CASP7 p.Asp255Glu

Q: How common is CASP7 p.Asp255Glu (c.765C>G) in the general population?

CASP7 p.Asp255Glu (c.765C>G) is common (popmax 44.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.765C>G · rs2227310 · VCV1246573

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 44.3%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -6.18	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 -1.3	GERP -3
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.049 · regional, not allelic
Overall
CADD	1.516	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 44.3% East Asian · 19,870/44,860 alleles

Filtering AF 43.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 43.6%

Overall 25.8% 416,166/1,613,424 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	44.3%	2
Amishnot grpmax-eligible	41.2%	2
Finnishnot grpmax-eligible	27.4%	4
Admixed American	26.7%	4
European (non-Finnish)	26.1%	4
Remaining individualsnot grpmax-eligible	24.6%	4
South Asian	23.6%	4
Middle Eastern	23%	4
Ashkenazi Jewishnot grpmax-eligible	19.4%	5
African / African-American	14.1%	7

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.Asp255Glu
Coding: c.765C>G
MANE Select: NM_001227
dbSNP: rs2227310
Type: single nucleotide variant
Location: chr10:113729393 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.05 · 47 PDB
Residue 255: a UniProt-annotated variant site (in); a turn

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

Similar variants

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
CASP7 p.Asp121Glu 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-asp255glu (accessed [today's date]).

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