Is ARAF p.Ala285= (c.855C>T) pathogenic?

ARAF p.Ala285= (c.855C>T) is classified Likely benign in ARAF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-01). Ultra-rare (popmax 0.014%, afr).

How common is ARAF p.Ala285= (c.855C>T) in the general population?

ARAF p.Ala285= (c.855C>T) is ultra-rare (popmax 0.014%, afr) (gnomAD).

ARAF p.Ala285=

c.855C>T · rs777457066 · VCV2660427

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.014%, afr)

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 -6.7
Overall
CADD	0.121	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.014% African / African-American · 8/57,135 alleles

Filtering AF 0.0069% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00503%

Overall 0.00182% 22/1,209,518 alleles · ultra-rare exomes 16/1,097,637 · genomes 6/111,881 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.014%	7,142
South Asian	0.00881%	11,354
Remaining individualsnot grpmax-eligible	0.0021%	47,581
European (non-Finnish)	0.000894%	111,869

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: ARAF
Protein: p.Ala285=
Coding: c.855C>T
MANE Select: NM_001654
dbSNP: rs777457066
Type: single nucleotide variant
Location: chrX:47567113 (GRCh38)
Structure: AlphaFold pLDDT 70.99 · 7 PDB
Residue 285: the 'disordered' region

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

Similar variants

ARAF p.His191Tyr Uncertain significance ★★ ⚠ same type
ARAF p.Ala334= Benign ★★ same type
ARAF p.Leu471= Benign ★★ same type
ARAF c.97-7C>T Uncertain significance ★ same type
ARAF p.Ala110Val Uncertain significance ★ ⚠ same type
ARAF p.Ala261Val Uncertain significance ★ ⚠ same type
ARAF p.Ala48Pro Uncertain significance ★ ⚠ same type
ARAF p.Arg151Cys 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/araf-p-ala285 (accessed [today's date]).

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