Is AP3S2 p.Ser79Phe (c.236C>T) pathogenic?

AP3S2 p.Ser79Phe (c.236C>T) is classified Uncertain significance in AP3S2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-03). AlphaMissense: likely pathogenic (0.6445); Absent from gnomAD v4.1.

How common is AP3S2 p.Ser79Phe (c.236C>T) in the general population?

AP3S2 p.Ser79Phe (c.236C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AP3S2 p.Ser79Phe (c.236C>T)?

AlphaMissense predicts likely pathogenic (score 0.6445) — an in-silico prediction, not a clinical call.

AP3S2 p.Ser79Phe

c.236C>T · VCV4115560

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6445 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6445	likely pathogenic
REVEL	0.39	indeterminate
SaProt	LLR -13.23	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 58 kb · p 0.79 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: AP3S2
Protein: p.Ser79Phe
Coding: c.236C>T
MANE Select: NM_005829
Type: single nucleotide variant
Location: chr15:89888558 (GRCh38)
Gene constraint: LOEUF 1.304 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.92

Full AP3S2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP3S2 p.Ala143Val Uncertain significance ★ ⚠ same type
AP3S2 p.Ala157Val Uncertain significance ★ ⚠ same type
AP3S2 p.Ala69Val Uncertain significance ★ ⚠ same type
AP3S2 p.Arg175Gln Uncertain significance ★ ⚠ same type
AP3S2 p.Arg18His Uncertain significance ★ same type
AP3S2 p.Arg33Gly Uncertain significance ★ ⚠ same type
AP3S2 p.Arg66Gln Uncertain significance ★ ⚠ same type
AP3S2 p.Asn178His 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/ap3s2-p-ser79phe (accessed [today's date]).

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