Is C7 p.Arg88Cys (c.262C>T) pathogenic?

C7 p.Arg88Cys (c.262C>T) is classified Uncertain significance in C7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-07). AlphaMissense: likely pathogenic (0.6536); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with C7 p.Arg88Cys (c.262C>T)?

C7 p.Arg88Cys (c.262C>T) is associated with Inborn genetic diseases (ClinVar).

How common is C7 p.Arg88Cys (c.262C>T) in the general population?

C7 p.Arg88Cys (c.262C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about C7 p.Arg88Cys (c.262C>T)?

AlphaMissense predicts likely pathogenic (score 0.6536) — an in-silico prediction, not a clinical call.

C7 p.Arg88Cys

c.262C>T · rs192439696 · VCV1462860

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6536 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6536	likely pathogenic · top 10% in C7
REVEL	0.668	pathogenic-leaning
SaProt	LLR -13.45	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 3.9	GERP 2.4, phastCons 1
Overall
CADD	27.8	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 0.00223% East Asian · 1/44,872 alleles

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

Overall 0.000372% 6/1,613,564 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,872
South Asian	0.0011%	91,064
European (non-Finnish)	0.000339%	294,901

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: C7
Protein: p.Arg88Cys
Coding: c.262C>T
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs192439696
Type: single nucleotide variant
Location: chr5:40934448 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB
Residue 88: an α-helix

Full C7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C7 p.Ala359Thr Uncertain significance ★★ ⚠ same condition
C7 p.Ala53Val Uncertain significance ★★ ⚠ same condition
C7 p.Ala611Pro Uncertain significance ★★ ⚠ same condition
C7 p.Ala839Thr Uncertain significance ★★ ⚠ same condition
C7 p.Arg220Trp Uncertain significance ★★ ⚠ same condition
C7 p.Arg226Ile Uncertain significance ★★ ⚠ same condition
C7 p.Arg293Gln Uncertain significance ★★ ⚠ same condition
C7 p.Arg372Gln Uncertain significance ★★ ⚠ same condition

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/c7-p-arg88cys (accessed [today's date]).

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