Is C5 p.Arg928Gln (c.2783G>A) pathogenic?

C5 p.Arg928Gln (c.2783G>A) is classified Benign/Likely benign in C5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-06). AlphaMissense: likely benign (0.1388); Low-frequency (popmax 2.75%, afr).

How common is C5 p.Arg928Gln (c.2783G>A) in the general population?

C5 p.Arg928Gln (c.2783G>A) is low-frequency (popmax 2.75%, afr) (gnomAD).

What do computational predictors say about C5 p.Arg928Gln (c.2783G>A)?

AlphaMissense predicts likely benign (score 0.1388) — an in-silico prediction, not a clinical call.

C5 p.Arg928Gln

c.2783G>A · rs41309892 · VCV783559

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1388 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.75%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1388	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -5.66	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 5.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 98 kb · p 1.2e-09 · regional, not allelic
Overall
CADD	26.6	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 2.75% African / African-American · 2,063/74,890 alleles

Filtering AF 2.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.62%

Overall 0.156% 2,510/1,610,228 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.75%	36
Admixed American	0.243%	411
Remaining individualsnot grpmax-eligible	0.216%	462
Middle Eastern	0.1%	997
South Asian	0.0132%	7,579
European (non-Finnish)	0.0126%	7,951

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.Arg928Gln
Coding: c.2783G>A
MANE Select: NM_001735
dbSNP: rs41309892
Type: single nucleotide variant
Location: chr9:120997554 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 49 PDB
Residue 928: a β-strand; a disulfide bond; a UniProt-annotated variant site (in c5d); a UniProt-annotated variant site (in)

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

Similar variants

C5 p.Arg928Ter Pathogenic ★ 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-arg928gln (accessed [today's date]).

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