Is ARVCF p.Arg34Trp (c.100C>T) pathogenic?

ARVCF p.Arg34Trp (c.100C>T) is classified Benign in ARVCF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-25). AlphaMissense: likely pathogenic (0.8928); Low-frequency (popmax 2.03%, afr).

How common is ARVCF p.Arg34Trp (c.100C>T) in the general population?

ARVCF p.Arg34Trp (c.100C>T) is low-frequency (popmax 2.03%, afr) (gnomAD).

What do computational predictors say about ARVCF p.Arg34Trp (c.100C>T)?

AlphaMissense predicts likely pathogenic (score 0.8928) — an in-silico prediction, not a clinical call.

ARVCF p.Arg34Trp

c.100C>T · rs116782322 · VCV714837

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8928 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.03%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8928	likely pathogenic
REVEL	0.236	benign-leaning
SaProt	LLR -14.96	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP -1.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.02 · regional, not allelic
Overall
CADD	27.1	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 2.03% African / African-American · 1,517/74,856 alleles

Filtering AF 1.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.91%

Overall 0.105% 1,677/1,600,828 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.03%	49
Remaining individualsnot grpmax-eligible	0.0888%	1,126
Admixed American	0.0799%	1,252
Middle Eastern	0.0331%	3,025
South Asian	0.00449%	22,256
European (non-Finnish)	0.00443%	22,576

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.Arg34Trp
Coding: c.100C>T
MANE Select: NM_001670
dbSNP: rs116782322
Type: single nucleotide variant
Location: chr22:19990695 (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.Arg34Gln 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
ARVCF c.1397-7C>T 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-arg34trp (accessed [today's date]).

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