Is YY1AP1 p.Pro682Ser (c.2044C>T) pathogenic?

YY1AP1 p.Pro682Ser (c.2044C>T) is classified Uncertain significance in YY1AP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.0811); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with YY1AP1 p.Pro682Ser (c.2044C>T)?

YY1AP1 p.Pro682Ser (c.2044C>T) is associated with Inborn genetic diseases (ClinVar).

How common is YY1AP1 p.Pro682Ser (c.2044C>T) in the general population?

YY1AP1 p.Pro682Ser (c.2044C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about YY1AP1 p.Pro682Ser (c.2044C>T)?

AlphaMissense predicts likely benign (score 0.0811) — an in-silico prediction, not a clinical call.

YY1AP1 p.Pro682Ser

c.2044C>T · VCV3471880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0811 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0811	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -4.98	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 0.88	GERP -3.1
Regional constraint	o/e 0.91	unconstrained · MANE · 11 kb · p 0.016 · regional, not allelic
Overall
CADD	2.04	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P728S vs ClinVar P682S) — verify the residue.

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: YY1AP1
Protein: p.Pro682Ser
Coding: c.2044C>T
MANE Select: NM_139119
Type: single nucleotide variant
Location: chr1:155659866 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.58
Residue 728 UniProt numbering: a UniProt-annotated variant site (in grng)

Full YY1AP1 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

YY1AP1 p.Gln75His Uncertain significance ★★ ⚠ same condition
YY1AP1 p.Ile135Met Uncertain significance ★★ ⚠ same condition
YY1AP1 p.Lys401Arg Likely benign ★★ same condition
YY1AP1 c.-11C>G Uncertain significance ★ ⚠ same condition
YY1AP1 c.-12G>T Uncertain significance ★ ⚠ same condition
YY1AP1 c.-2T>C Uncertain significance ★ same condition
YY1AP1 p.Ala206Ser Uncertain significance ★ ⚠ same condition
YY1AP1 p.Ala240Thr 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/yy1ap1-p-pro682ser (accessed [today's date]).

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