Is C5 p.Arg32Cys (c.94C>T) pathogenic?

C5 p.Arg32Cys (c.94C>T) is classified Uncertain significance in C5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: likely benign (0.1196); Ultra-rare (popmax 0.0383%, amr).

How common is C5 p.Arg32Cys (c.94C>T) in the general population?

C5 p.Arg32Cys (c.94C>T) is ultra-rare (popmax 0.0383%, amr) (gnomAD).

What do computational predictors say about C5 p.Arg32Cys (c.94C>T)?

AlphaMissense predicts likely benign (score 0.1196) — an in-silico prediction, not a clinical call.

C5 p.Arg32Cys

c.94C>T · VCV4705662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1196 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1196	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -11.91	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 1.1	GERP -0.88
Regional constraint	o/e 0.86	unconstrained · MANE · 98 kb · p 1.2e-09 · regional, not allelic
Overall
CADD	24.2	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 0.0383% Admixed American · 23/59,978 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.0023% 37/1,611,780 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0383%	2,608
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,782
African / African-American	0.00134%	74,788
European (non-Finnish)	0.000849%	117,843

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: C5
Protein: p.Arg32Cys
Coding: c.94C>T
MANE Select: NM_001735
Type: single nucleotide variant
Location: chr9:121046355 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 32: a UniProt-annotated variant site (in c5d); a β-strand

Full C5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C5 p.Arg32His Conflicting classifications of pathogenicity ★ ⚠ same residue
C5 c.2257+1G>A Likely pathogenic ★★ same type
C5 c.4679-2A>G Likely pathogenic ★★ same type
C5 p.Arg1476Ter Pathogenic/Likely pathogenic ★★ same type
C5 p.Gln19Ter Pathogenic ★★ same type
C5 p.Glu1437Ter Pathogenic/Likely pathogenic ★★ same type
C5 p.Trp469Ter Pathogenic/Likely pathogenic ★★ same type
C5 c.2059+3A>G 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/c5-p-arg32cys (accessed [today's date]).

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