Is ARVCF p.Arg394= (c.1182G>C) pathogenic?

ARVCF p.Arg394= (c.1182G>C) is classified Benign in ARVCF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-05). Common (popmax 5.27%, eas) — too common for a highly-penetrant pathogenic allele.

ARVCF p.Arg394=

Q: How common is ARVCF p.Arg394= (c.1182G>C) in the general population?

ARVCF p.Arg394= (c.1182G>C) is common (popmax 5.27%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1182G>C · rs74544696 · VCV1180930

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.27%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.68	GERP -3.7, phastCons 0.003
Overall
CADD	0.516	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.27% East Asian · 2,315/43,924 alleles

Filtering AF 5.09% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.02%

Overall 2.09% 33,361/1,595,190 alleles · common exomes 29,766/1,442,842 · genomes 3,595/152,348 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	5.27%	19
South Asian	3.5%	29
African / African-American	3.09%	32
Middle Eastern	2.24%	45
Remaining individualsnot grpmax-eligible	2.16%	46
Admixed American	2.01%	50
Ashkenazi Jewishnot grpmax-eligible	1.96%	51
European (non-Finnish)	1.88%	53
Finnishnot grpmax-eligible	0.735%	136

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: ARVCF
Protein: p.Arg394=
Coding: c.1182G>C
MANE Select: NM_001670
dbSNP: rs74544696
Type: single nucleotide variant
Location: chr22:19979957 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.73

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

Similar variants

ARVCF p.Arg394Gln Uncertain significance ★ ⚠ same residue
ARVCF p.Arg394Trp Uncertain significance ★ ⚠ same residue
ARVCF p.Gly172Ser Uncertain significance ★★ ⚠ same type
ARVCF p.Val958Ile Uncertain significance ★★ ⚠ same type
ARVCF c.1396+18A>G Benign ★★ same type
ARVCF c.1396+198C>T Benign ★★ same type
ARVCF c.1396+40G>A Benign ★★ same type
ARVCF c.1397-146G>A Benign ★★ 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/arvcf-p-arg394 (accessed [today's date]).

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