Is AP1S2 p.Ser96= (c.288T>C) pathogenic?

AP1S2 p.Ser96= (c.288T>C) is classified Benign/Likely benign in AP1S2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Low-frequency (popmax 4.77%, afr); Associated with Inborn genetic diseases.

What condition is associated with AP1S2 p.Ser96= (c.288T>C)?

AP1S2 p.Ser96= (c.288T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AP1S2 p.Ser96= (c.288T>C) in the general population?

AP1S2 p.Ser96= (c.288T>C) is low-frequency (popmax 4.77%, afr) (gnomAD).

AP1S2 p.Ser96=

c.288T>C · rs61741688 · VCV157714

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.77%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.387	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -0.57, phastCons 0.99
Overall
CADD	10.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.77% African / African-American · 2,710/56,839 alleles

Filtering AF 4.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.56%

Overall 0.291% 3,462/1,190,496 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.77%	21
Ashkenazi Jewishnot grpmax-eligible	0.726%	138
Admixed American	0.426%	234
Remaining individualsnot grpmax-eligible	0.335%	299
Middle Eastern	0.326%	307
European (non-Finnish)	0.0252%	3,970
South Asian	0.0106%	9,399

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: AP1S2
Protein: p.Ser96=
Coding: c.288T>C
MANE Select: NM_001272071
dbSNP: rs61741688
Type: single nucleotide variant
Location: chrX:15845903 (GRCh38)
Structure: AlphaFold pLDDT 94.36

Full AP1S2 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

AP1S2 p.Gly158Arg Uncertain significance ★★ ⚠ same condition
AP1S2 p.Ile134Thr Uncertain significance ★★ ⚠ same condition
AP1S2 p.Ile82Val Uncertain significance ★★ ⚠ same condition
AP1S2 p.Leu54Val Uncertain significance ★★ ⚠ same condition
AP1S2 c.289-8C>T Benign/Likely benign ★★ same condition
AP1S2 p.Val38Ile Benign/Likely benign ★★ same condition
AP1S2 p.Ser23Ter Pathogenic ★ same condition
AP1S2 c.*1C>T 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/ap1s2-p-ser96 (accessed [today's date]).

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