Is YY1AP1 p.Ser727Pro (c.2179T>C) pathogenic?

YY1AP1 p.Ser727Pro (c.2179T>C) is classified Likely benign in YY1AP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely benign (0.0644); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with YY1AP1 p.Ser727Pro (c.2179T>C)?

YY1AP1 p.Ser727Pro (c.2179T>C) is associated with Inborn genetic diseases (ClinVar).

How common is YY1AP1 p.Ser727Pro (c.2179T>C) in the general population?

YY1AP1 p.Ser727Pro (c.2179T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about YY1AP1 p.Ser727Pro (c.2179T>C)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

YY1AP1 p.Ser727Pro

c.2179T>C · rs556811436 · VCV3191696

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -6.69	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 -2.9	GERP -2.8
Regional constraint	o/e 0.91	unconstrained · MANE · 11 kb · p 0.016 · regional, not allelic
Overall
CADD	0.075	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 S773P vs ClinVar S727P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,024 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,614,160 alleles · very rare exomes 3/1,461,892 · genomes 0/152,268 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,512
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Ser727Pro
Coding: c.2179T>C
MANE Select: NM_139119
dbSNP: rs556811436
Type: single nucleotide variant
Location: chr1:155659731 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.58
Residue 773 UniProt numbering: a UniProt-annotated variant site (in grng); the 'disordered' region

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.Ser727Thr Uncertain significance ★ ⚠ same residue
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

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-ser727pro (accessed [today's date]).

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