Is C8B p.Arg242Cys (c.724C>T) pathogenic?

C8B p.Arg242Cys (c.724C>T) is classified Likely benign in C8B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-22). AlphaMissense: likely benign (0.1404); Rare (popmax 0.288%, afr).

How common is C8B p.Arg242Cys (c.724C>T) in the general population?

C8B p.Arg242Cys (c.724C>T) is rare (popmax 0.288%, afr) (gnomAD).

What do computational predictors say about C8B p.Arg242Cys (c.724C>T)?

AlphaMissense predicts likely benign (score 0.1404) — an in-silico prediction, not a clinical call.

C8B p.Arg242Cys

c.724C>T · rs150146785 · VCV745025

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1404 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.288%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1404	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -12.06	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -4.2
Regional constraint	o/e 1.09	unconstrained · MANE · 37 kb · p 0.016 · regional, not allelic
Overall
CADD	20.0	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 0.288% African / African-American · 216/75,002 alleles

Filtering AF 0.257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.244%

Overall 0.0176% 284/1,613,824 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.288%	347
Admixed American	0.0417%	2,400
Remaining individualsnot grpmax-eligible	0.04%	2,500
South Asian	0.00878%	11,385
European (non-Finnish)	0.000848%	117,989

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: C8B
Protein: p.Arg242Cys
Coding: c.724C>T
MANE Select: NM_000066
dbSNP: rs150146785
Type: single nucleotide variant
Location: chr1:56949695 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.99 · 8 PDB
Residue 242: a UniProt-annotated variant site (in c8d2); a turn; the macpf domain

Full C8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C8B p.Arg242His Conflicting classifications of pathogenicity ★ ⚠ same residue
C8B p.Arg242= Likely benign ★ same residue
C8B p.Arg284Ter Pathogenic ★★ same type
C8B p.Arg428Ter Pathogenic ★★ same type
C8B p.Cys508Ter Pathogenic/Likely pathogenic ★★ same type
C8B p.Gln91Ter Pathogenic/Likely pathogenic ★★ same type
C8B p.Trp9Ter Pathogenic ★★ same type
C8B p.Ala21Thr 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/c8b-p-arg242cys (accessed [today's date]).

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