Is C8B p.Ser50Arg (c.150C>G) pathogenic?

C8B p.Ser50Arg (c.150C>G) is classified Conflicting classifications of pathogenicity in C8B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-06). AlphaMissense: likely benign (0.1735); Rare (popmax 0.265%, afr).

How common is C8B p.Ser50Arg (c.150C>G) in the general population?

C8B p.Ser50Arg (c.150C>G) is rare (popmax 0.265%, afr) (gnomAD).

What do computational predictors say about C8B p.Ser50Arg (c.150C>G)?

AlphaMissense predicts likely benign (score 0.1735) — an in-silico prediction, not a clinical call.

C8B p.Ser50Arg

c.150C>G · rs150386354 · VCV1647919

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1735 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.265%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1735	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.24	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 0.6	GERP -4.3, phastCons 0.58
Regional constraint	o/e 1.09	unconstrained · MANE · 37 kb · p 0.016 · regional, not allelic
Overall
CADD	6.002	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 0.265% African / African-American · 199/75,038 alleles

Filtering AF 0.235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.223%

Overall 0.0181% 292/1,614,136 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.265%	377
Middle Eastern	0.066%	1,516
Admixed American	0.0433%	2,309
Remaining individualsnot grpmax-eligible	0.0352%	2,841
South Asian	0.00549%	18,215
European (non-Finnish)	0.00305%	32,778

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.Ser50Arg
Coding: c.150C>G
MANE Select: NM_000066
dbSNP: rs150386354
Type: single nucleotide variant
Location: chr1:56960119 (GRCh38)
Gene constraint: LOEUF 1.18 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.99 · 8 PDB

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

Similar variants

C8B p.Ser50fs Pathogenic ★ 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
C8B p.Ala446Val 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-ser50arg (accessed [today's date]).

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