Is YY1AP1 p.Phe143Ser (c.428T>C) pathogenic?

YY1AP1 p.Phe143Ser (c.428T>C) is classified Uncertain significance in YY1AP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely pathogenic (0.9861); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with YY1AP1 p.Phe143Ser (c.428T>C)?

YY1AP1 p.Phe143Ser (c.428T>C) is associated with Inborn genetic diseases (ClinVar).

How common is YY1AP1 p.Phe143Ser (c.428T>C) in the general population?

YY1AP1 p.Phe143Ser (c.428T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about YY1AP1 p.Phe143Ser (c.428T>C)?

AlphaMissense predicts likely pathogenic (score 0.9861) — an in-silico prediction, not a clinical call.

YY1AP1 p.Phe143Ser

c.428T>C · VCV3471883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9861 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9861	likely pathogenic · top 1% in YY1AP1
REVEL	0.317	indeterminate
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 7,777 bp · p 0.64 · regional, not allelic
Overall
CADD	27.5	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 F209S vs ClinVar F143S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,918 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,068 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,918
European (non-Finnish)	0.000339%	295,012

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.Phe143Ser
Coding: c.428T>C
MANE Select: NM_139119
Type: single nucleotide variant
Location: chr1:155672715 (GRCh38)
Gene constraint: LOEUF 1.319 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.58

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-phe143ser (accessed [today's date]).

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