Is ARAF p.Ser162Pro (c.484T>C) pathogenic?

ARAF p.Ser162Pro (c.484T>C) is classified Uncertain significance in ARAF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-09). AlphaMissense: likely benign (0.0619); Absent from gnomAD v4.1.

How common is ARAF p.Ser162Pro (c.484T>C) in the general population?

ARAF p.Ser162Pro (c.484T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARAF p.Ser162Pro (c.484T>C)?

AlphaMissense predicts likely benign (score 0.0619) — an in-silico prediction, not a clinical call.

ARAF p.Ser162Pro

c.484T>C · rs2519673611 · VCV2260066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0619 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0619	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 2,114 bp · p 0.077 · regional, not allelic
Overall
CADD	17.06	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: ARAF
Protein: p.Ser162Pro
Coding: c.484T>C
MANE Select: NM_001654
dbSNP: rs2519673611
Type: single nucleotide variant
Location: chrX:47565277 (GRCh38)
Structure: AlphaFold pLDDT 70.99 · 7 PDB
Residue 162: a modified residue (phosphoserine); 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-ser162pro (accessed [today's date]).

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