Is ARVCF p.Leu826Val (c.2476C>G) pathogenic?

ARVCF p.Leu826Val (c.2476C>G) is classified Uncertain significance in ARVCF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: ambiguous (0.4506); Absent from gnomAD v4.1.

How common is ARVCF p.Leu826Val (c.2476C>G) in the general population?

ARVCF p.Leu826Val (c.2476C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARVCF p.Leu826Val (c.2476C>G)?

AlphaMissense predicts ambiguous (score 0.4506) — an in-silico prediction, not a clinical call.

ARVCF p.Leu826Val

c.2476C>G · rs201679264 · VCV2273269

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4506 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4506	ambiguous
REVEL	0.415	indeterminate
SaProt	LLR -13.71	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP -0.79, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.02 · regional, not allelic
Overall
CADD	22.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARVCF
Protein: p.Leu826Val
Coding: c.2476C>G
MANE Select: NM_001670
dbSNP: rs201679264
Type: single nucleotide variant
Location: chr22:19972999 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.73
Residue 826: the 'required for interaction with rna-binding proteins ddx5, hnrnph2 and srsf1 and with mrnas' 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-leu826val (accessed [today's date]).

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