Is USP24 p.Ser996Pro (c.2986T>C) pathogenic?

USP24 p.Ser996Pro (c.2986T>C) is classified Uncertain significance in USP24 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely pathogenic (0.6975); Very rare (popmax 0.00521%, nfe).

How common is USP24 p.Ser996Pro (c.2986T>C) in the general population?

USP24 p.Ser996Pro (c.2986T>C) is very rare (popmax 0.00521%, nfe) (gnomAD).

What do computational predictors say about USP24 p.Ser996Pro (c.2986T>C)?

AlphaMissense predicts likely pathogenic (score 0.6975) — an in-silico prediction, not a clinical call.

USP24 p.Ser996Pro

c.2986T>C · rs2523827981 · VCV3187283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6975 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00521%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6975	likely pathogenic
REVEL	0.097	moderately benign-leaning
SaProt	LLR -12.69	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2.3, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 47 kb · p 2e-20 · regional, not allelic
Overall
CADD	22.8	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 0.00521% European (non-Finnish) · 61/1,171,010 alleles

Filtering AF 0.00413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00429% 62/1,445,390 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00521%	19,197
Remaining individualsnot grpmax-eligible	0.00162%	61,848

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: USP24
Protein: p.Ser996Pro
Coding: c.2986T>C
MANE Select: NM_015306
dbSNP: rs2523827981
Type: single nucleotide variant
Location: chr1:55137847 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.15

Full USP24 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP24 p.Ala1561= Benign ★★ same type
USP24 p.His2523= Benign ★★ same type
USP24 p.Leu726= Benign ★★ same type
USP24 p.Lys653= Benign ★★ same type
USP24 p.Thr158Ala Benign ★★ same type
USP24 c.6554+1G>A Uncertain significance ★ same type
USP24 p.Ala1077Val Uncertain significance ★ ⚠ same type
USP24 p.Ala1267Thr 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/usp24-p-ser996pro (accessed [today's date]).

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