Is WAC p.Ser384Pro (c.1150T>C) pathogenic?

WAC p.Ser384Pro (c.1150T>C) is classified Uncertain significance in WAC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: ambiguous (0.4513); Very rare (popmax 0.000341%, nfe); Associated with Inborn genetic diseases.

What condition is associated with WAC p.Ser384Pro (c.1150T>C)?

WAC p.Ser384Pro (c.1150T>C) is associated with Inborn genetic diseases (ClinVar).

How common is WAC p.Ser384Pro (c.1150T>C) in the general population?

WAC p.Ser384Pro (c.1150T>C) is very rare (popmax 0.000341%, nfe) (gnomAD).

What do computational predictors say about WAC p.Ser384Pro (c.1150T>C)?

AlphaMissense predicts ambiguous (score 0.4513) — an in-silico prediction, not a clinical call.

WAC p.Ser384Pro

c.1150T>C · VCV4200053

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4513 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000341%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4513	ambiguous
REVEL	0.202	benign-leaning
SaProt	LLR -10.02	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 83 kb · p 0.6 · regional, not allelic
Overall
CADD	25.9	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

Grpmax group 0.000341% European (non-Finnish) · 4/1,171,630 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00025% 4/1,598,146 alleles · very rare exomes 4/1,445,774 · genomes 0/152,372 · joint denominator

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.Ser384Pro
Coding: c.1150T>C
MANE Select: NM_016628
Type: single nucleotide variant
Location: chr10:28608416 (GRCh38)
Gene constraint: LOEUF 0.248 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.71
Residue 384: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WAC p.Arg550Ter Pathogenic ★★ same condition
WAC p.Ala237Val Uncertain significance ★★ ⚠ same condition
WAC p.Gln358Pro Uncertain significance ★★ ⚠ same condition
WAC p.His274Asn Uncertain significance ★★ ⚠ same condition
WAC p.His562Leu Uncertain significance ★★ same condition
WAC p.Leu426Pro Uncertain significance ★★ ⚠ same condition
WAC p.Leu605Phe Uncertain significance ★★ ⚠ same condition
WAC p.Ser493Leu Uncertain significance ★★ ⚠ 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-ser384pro (accessed [today's date]).

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