Is AP1S2 p.Ile82Val (c.244A>G) pathogenic?

AP1S2 p.Ile82Val (c.244A>G) is classified Uncertain significance in AP1S2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-07). AlphaMissense: likely benign (0.0703); Very rare (popmax 0.00157%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AP1S2 p.Ile82Val (c.244A>G)?

AP1S2 p.Ile82Val (c.244A>G) is associated with Inborn genetic diseases (ClinVar).

How common is AP1S2 p.Ile82Val (c.244A>G) in the general population?

AP1S2 p.Ile82Val (c.244A>G) is very rare (popmax 0.00157%, nfe) (gnomAD).

What do computational predictors say about AP1S2 p.Ile82Val (c.244A>G)?

AlphaMissense predicts likely benign (score 0.0703) — an in-silico prediction, not a clinical call.

AP1S2 p.Ile82Val

c.244A>G · rs1399162998 · VCV1947968

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0703 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00157%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0703	likely benign
REVEL	0.395	indeterminate
SaProt	LLR -8.49	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.07	constrained · MANE · 556 bp · p 3.2e-09 · regional, not allelic
Overall
CADD	20.5	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

Grpmax group 0.00157% European (non-Finnish) · 14/890,731 alleles

Filtering AF 0.000912% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000713%

Overall 0.00116% 14/1,205,333 alleles · very rare

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.Ile82Val
Coding: c.244A>G
MANE Select: NM_001272071
dbSNP: rs1399162998
Type: single nucleotide variant
Location: chrX:15845947 (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.Leu54Val Uncertain significance ★★ ⚠ same condition
AP1S2 c.289-8C>T Benign/Likely benign ★★ same condition
AP1S2 p.Ser96= 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-ile82val (accessed [today's date]).

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