Is AP2S1 p.Ala79Val (c.236C>T) pathogenic?

AP2S1 p.Ala79Val (c.236C>T) is classified Uncertain significance in AP2S1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). AlphaMissense: likely benign (0.2035); Absent from gnomAD v4.1.

How common is AP2S1 p.Ala79Val (c.236C>T) in the general population?

AP2S1 p.Ala79Val (c.236C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP2S1 p.Ala79Val (c.236C>T)?

AlphaMissense predicts likely benign (score 0.2035) — an in-silico prediction, not a clinical call.

AP2S1 p.Ala79Val

c.236C>T · rs2514059234 · VCV2998564

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2035 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2035	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -8.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 12 kb · p 2.2e-20 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: AP2S1
Protein: p.Ala79Val
Coding: c.236C>T
MANE Select: NM_004069
dbSNP: rs2514059234
Type: single nucleotide variant
Location: chr19:46839496 (GRCh38)
Gene constraint: LOEUF 0.478 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 97.03 · 1 PDB
Residue 79: an α-helix

Full AP2S1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP2S1 p.Arg15Cys Pathogenic ★★ same type
AP2S1 p.Arg15His Pathogenic/Likely pathogenic ★★ same type
AP2S1 p.Arg15Leu Pathogenic ★★ same type
AP2S1 c.153+5C>T Uncertain significance ★★ same type
AP2S1 p.Arg60His Uncertain significance ★★ ⚠ same type
AP2S1 p.Gln22His Uncertain significance ★★ ⚠ same type
AP2S1 p.Ile84Val Uncertain significance ★★ ⚠ same type
AP2S1 p.Thr112Met 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/ap2s1-p-ala79val (accessed [today's date]).

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