Is YY1AP1 p.Ala559Pro (c.1675G>C) pathogenic?

YY1AP1 p.Ala559Pro (c.1675G>C) is classified Uncertain significance in YY1AP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: ambiguous (0.499); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with YY1AP1 p.Ala559Pro (c.1675G>C)?

YY1AP1 p.Ala559Pro (c.1675G>C) is associated with Inborn genetic diseases (ClinVar).

How common is YY1AP1 p.Ala559Pro (c.1675G>C) in the general population?

YY1AP1 p.Ala559Pro (c.1675G>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about YY1AP1 p.Ala559Pro (c.1675G>C)?

AlphaMissense predicts ambiguous (score 0.499) — an in-silico prediction, not a clinical call.

YY1AP1 p.Ala559Pro

c.1675G>C · VCV3983292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.499 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.499	ambiguous
REVEL	0.184	benign-leaning
SaProt	LLR -6.18	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 11 kb · p 0.016 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A605P vs ClinVar A559P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,900 alleles

Overall 6.2e-05% 1/1,614,054 alleles · very rare exomes 0/1,461,894 · genomes 1/152,160 · joint denominator

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: YY1AP1
Protein: p.Ala559Pro
Coding: c.1675G>C
MANE Select: NM_139119
Type: single nucleotide variant
Location: chr1:155660235 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.58
Residue 605 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-ala559pro (accessed [today's date]).

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