Is ARVCF p.Pro937= (c.2811C>T) pathogenic?

ARVCF p.Pro937= (c.2811C>T) is classified Benign in ARVCF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-04). Common (popmax 13.8%, afr) — too common for a highly-penetrant pathogenic allele.

ARVCF p.Pro937=

Q: How common is ARVCF p.Pro937= (c.2811C>T) in the general population?

ARVCF p.Pro937= (c.2811C>T) is common (popmax 13.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2811C>T · rs5993890 · VCV1242019

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 13.8%, afr) — 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 -5.8	GERP -3
Overall
CADD	0.726	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.8% African / African-American · 10,131/73,592 alleles

Filtering AF 13.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.5%

Overall 5.56% 86,530/1,555,452 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.8%	7
South Asian	9.86%	10
Ashkenazi Jewishnot grpmax-eligible	8.82%	11
Amishnot grpmax-eligible	8.77%	11
Middle Eastern	7.66%	13
Admixed American	7.32%	14
Remaining individualsnot grpmax-eligible	6.61%	15
European (non-Finnish)	4.73%	21
East Asian	3.02%	33
Finnishnot grpmax-eligible	2.76%	36

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.Pro937=
Coding: c.2811C>T
MANE Select: NM_001670
dbSNP: rs5993890
Type: single nucleotide variant
Location: chr22:19971306 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.73
Residue 937: the 'required for interaction with rna-binding proteins ddx5, hnrnph2 and srsf1 and with mrnas' region; the 'disordered' region

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

Similar variants

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
ARVCF c.1397-7C>T Benign ★★ same type
ARVCF c.1871-172A>C 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-pro937 (accessed [today's date]).

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