Is WAC p.Arg169= (c.507A>G) pathogenic?

WAC p.Arg169= (c.507A>G) is classified Likely benign in WAC (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-29). Very rare (popmax 0.00809%, afr); Associated with intellectual disability.

What condition is associated with WAC p.Arg169= (c.507A>G)?

WAC p.Arg169= (c.507A>G) is associated with intellectual disability (ClinVar).

How common is WAC p.Arg169= (c.507A>G) in the general population?

WAC p.Arg169= (c.507A>G) is very rare (popmax 0.00809%, afr) (gnomAD).

WAC p.Arg169=

c.507A>G · VCV4075296

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00809%, afr)

Conditions

intellectual disability

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 4.7	GERP 1.6, phastCons 1
Overall
CADD	11.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00809% African / African-American · 6/74,154 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0024%

Overall 0.000686% 11/1,602,958 alleles · very rare exomes 6/1,450,800 · genomes 5/152,158 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00809%	12,359
European (non-Finnish)	0.000425%	235,081

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: WAC
Protein: p.Arg169=
Coding: c.507A>G
MANE Select: NM_016628
Type: single nucleotide variant
Location: chr10:28590729 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 169: the 'disordered' region; a UniProt-annotated variant site (found in a patient with severe intellectual disability; likely pathogenic)

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WAC p.Arg613Ter Pathogenic/Likely pathogenic ★★ same condition
WAC p.Arg169fs Likely pathogenic ★ same residue
WAC p.Pro55Ser Uncertain significance ★ ⚠ same condition
WAC p.Tyr148= Uncertain significance ★ same condition
WAC p.Tyr148Ser Uncertain significance ★ ⚠ same condition
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

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-arg169 (accessed [today's date]).

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