Is ARV1 p.Phe176= (c.528C>T) pathogenic?

ARV1 p.Phe176= (c.528C>T) is classified Benign/Likely benign in ARV1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). Rare (popmax 0.292%, afr).

How common is ARV1 p.Phe176= (c.528C>T) in the general population?

ARV1 p.Phe176= (c.528C>T) is rare (popmax 0.292%, afr) (gnomAD).

ARV1 p.Phe176=

c.528C>T · rs35606565 · VCV742517

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.292%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.047	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -1.7
Overall
CADD	5.339	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.292% African / African-American · 219/75,012 alleles

Filtering AF 0.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.248%

Overall 0.0154% 249/1,614,062 alleles · rare exomes 116/1,461,844 · genomes 133/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.292%	343
Admixed American	0.0217%	4,617
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Middle Eastern	0.0165%	6,060
European (non-Finnish)	0.000254%	393,335

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: ARV1
Protein: p.Phe176=
Coding: c.528C>T
MANE Select: NM_022786
dbSNP: rs35606565
Type: single nucleotide variant
Location: chr1:230995839 (GRCh38)
Gene constraint: LOEUF 1.131 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.17

Full ARV1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARV1 c.175-2A>G Likely pathogenic ★★ same type
ARV1 c.294+1G>A Pathogenic ★★ same type
ARV1 c.*4+1G>A Uncertain significance ★★ same type
ARV1 p.Arg231Cys Uncertain significance ★★ ⚠ same type
ARV1 p.Asn219Asp Uncertain significance ★★ ⚠ same type
ARV1 p.Asn219Thr Uncertain significance ★★ ⚠ same type
ARV1 p.Asp72Asn Uncertain significance ★★ ⚠ same type
ARV1 p.Cys34Tyr Uncertain significance ★★ ⚠ 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/arv1-p-phe176 (accessed [today's date]).

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