Is WAC p.Pro483Arg (c.1448C>G) pathogenic?

WAC p.Pro483Arg (c.1448C>G) is classified Uncertain significance in WAC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.2671); Absent from gnomAD v4.1.

How common is WAC p.Pro483Arg (c.1448C>G) in the general population?

WAC p.Pro483Arg (c.1448C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WAC p.Pro483Arg (c.1448C>G)?

AlphaMissense predicts likely benign (score 0.2671) — an in-silico prediction, not a clinical call.

WAC p.Pro483Arg

c.1448C>G · rs147282072 · VCV1723050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2671 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2671	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -11.92	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 83 kb · p 0.6 · regional, not allelic
Overall
CADD	27.6	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: WAC
Protein: p.Pro483Arg
Coding: c.1448C>G
MANE Select: NM_016628
dbSNP: rs147282072
Type: single nucleotide variant
Location: chr10:28614577 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 483: a UniProt-annotated variant site (found in a patient with severe intellectual disability; likely pathogenic); the 'disordered' region

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

Similar variants

WAC p.Pro483Leu Uncertain significance ★ ⚠ same residue
WAC c.1437+1G>A Pathogenic/Likely pathogenic ★★ same type
WAC c.1746+2T>C Pathogenic ★★ same type
WAC c.381+1G>T Likely pathogenic ★★ same type
WAC p.Arg151Ter Pathogenic ★★ same type
WAC p.Arg47Ter Pathogenic ★★ same type
WAC p.Arg513Ter Pathogenic ★★ same type
WAC p.Arg550Ter Pathogenic ★★ 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/wac-p-pro483arg (accessed [today's date]).

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