Is C7 p.Cys128Arg (c.382T>C) pathogenic?

C7 p.Cys128Arg (c.382T>C) is classified Benign/Likely benign in C7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-06). AlphaMissense: likely pathogenic (0.9749); Common (popmax 8.96%, amr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about C7 p.Cys128Arg (c.382T>C)?

AlphaMissense predicts likely pathogenic (score 0.9749) — an in-silico prediction, not a clinical call.

C7 p.Cys128Arg

Q: How common is C7 p.Cys128Arg (c.382T>C) in the general population?

C7 p.Cys128Arg (c.382T>C) is common (popmax 8.96%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.382T>C · rs2271708 · VCV1165525

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9749 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.96%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9749	likely pathogenic · top 1% in C7
REVEL	0.394	indeterminate
SaProt	LLR -9.95	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Overall
CADD	23.8	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 8.96% Admixed American · 5,362/59,876 alleles

Filtering AF 8.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.67%

Overall 1.14% 18,440/1,613,254 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	8.96%	11
East Asian	4.3%	23
South Asian	2.46%	41
Finnishnot grpmax-eligible	1.43%	70
Remaining individualsnot grpmax-eligible	1.11%	90
Middle Eastern	0.809%	124
Ashkenazi Jewishnot grpmax-eligible	0.764%	131
European (non-Finnish)	0.585%	171
African / African-American	0.177%	564

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.Cys128Arg
Coding: c.382T>C
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs2271708
Type: single nucleotide variant
Location: chr5:40936439 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

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

Similar variants

C7 c.281-1G>T Pathogenic/Likely pathogenic ★★ same type
C7 c.63-1G>A Pathogenic ★★ same type
C7 c.739-2A>G Likely pathogenic ★★ same type
C7 p.Arg402Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Gln271Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Gly379Arg Pathogenic/Likely pathogenic ★★ same type
C7 p.Trp205Ter Pathogenic/Likely pathogenic ★★ same type
C7 p.Ala359Thr 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/c7-p-cys128arg (accessed [today's date]).

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