Is C7 p.Arg293Gln (c.878G>A) pathogenic?

C7 p.Arg293Gln (c.878G>A) is classified Uncertain significance in C7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-17). AlphaMissense: likely benign (0.1192); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with C7 p.Arg293Gln (c.878G>A)?

C7 p.Arg293Gln (c.878G>A) is associated with Inborn genetic diseases (ClinVar).

How common is C7 p.Arg293Gln (c.878G>A) in the general population?

C7 p.Arg293Gln (c.878G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about C7 p.Arg293Gln (c.878G>A)?

AlphaMissense predicts likely benign (score 0.1192) — an in-silico prediction, not a clinical call.

C7 p.Arg293Gln

c.878G>A · rs764221802 · VCV1044036

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1192 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1192	likely benign
REVEL	0.744	pathogenic-leaning
SaProt	LLR -7.04	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.4, phastCons 1
Overall
CADD	25.7	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 0.00329% South Asian · 3/91,076 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00109% 16/1,461,520 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,359
Admixed American	0.00167%	59,982
African / African-American	0.00133%	74,990
European (non-Finnish)	0.000932%	107,251

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.Arg293Gln
Coding: c.878G>A
MANE Select: NM_001565 · reported on NM_000587
dbSNP: rs764221802
Type: single nucleotide variant
Location: chr5:40947741 (GRCh38)
Structure: AlphaFold pLDDT 89.67 · 6 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

C7 p.Arg293Ter Pathogenic ★ same residue
C7 p.Ala359Thr Uncertain significance ★★ ⚠ same condition
C7 p.Ala53Val Uncertain significance ★★ ⚠ same condition
C7 p.Ala611Pro Uncertain significance ★★ ⚠ same condition
C7 p.Ala839Thr Uncertain significance ★★ ⚠ same condition
C7 p.Arg220Trp Uncertain significance ★★ ⚠ same condition
C7 p.Arg226Ile Uncertain significance ★★ ⚠ same condition
C7 p.Arg372Gln Uncertain significance ★★ ⚠ same condition

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-arg293gln (accessed [today's date]).

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