Is WAC p.Arg613Ter (c.1837C>T) pathogenic?

WAC p.Arg613Ter (c.1837C>T) is classified Pathogenic/Likely pathogenic in WAC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-25). Absent from gnomAD v4.1; Associated with Neurodevelopmental abnormality.

What condition is associated with WAC p.Arg613Ter (c.1837C>T)?

WAC p.Arg613Ter (c.1837C>T) is associated with Neurodevelopmental abnormality, intellectual disability, DeSanto-Shinawi syndrome due to WAC point mutation (ClinVar).

How common is WAC p.Arg613Ter (c.1837C>T) in the general population?

WAC p.Arg613Ter (c.1837C>T) is absent from gnomAD v4.1 (gnomAD).

WAC p.Arg613Ter

c.1837C>T · rs1085307480 · VCV426162

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Neurodevelopmental abnormality

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (13 of 14, 37 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.11, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Arg613Ter
Coding: c.1837C>T
MANE Select: NM_016628
dbSNP: rs1085307480
Type: single nucleotide variant
Location: chr10:28617747 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 613: 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

Neurodevelopmental abnormality — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability DeSanto-Shinawi syndrome due to WAC point mutation

Similar variants

WAC c.1437+1G>A Pathogenic/Likely pathogenic ★★ same condition
WAC c.381+1G>T Likely pathogenic ★★ same condition
WAC p.Arg151Ter Pathogenic ★★ same condition
WAC p.Arg47Ter Pathogenic ★★ same condition
WAC p.Arg513Ter Pathogenic ★★ same condition
WAC p.Arg550Ter Pathogenic ★★ same condition
WAC p.Arg622Ter Pathogenic/Likely pathogenic ★★ same condition
WAC p.Gln170Ter Pathogenic ★★ same condition

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-arg613ter (accessed [today's date]).

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