Is TAF4 p.Pro75Ser (c.223C>T) pathogenic?

TAF4 p.Pro75Ser (c.223C>T) is classified Uncertain significance in TAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-07). AlphaMissense: likely benign (0.0949); Rare (popmax 0.163%, eas); Associated with Inborn genetic diseases.

What condition is associated with TAF4 p.Pro75Ser (c.223C>T)?

TAF4 p.Pro75Ser (c.223C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TAF4 p.Pro75Ser (c.223C>T) in the general population?

TAF4 p.Pro75Ser (c.223C>T) is rare (popmax 0.163%, eas) (gnomAD).

What do computational predictors say about TAF4 p.Pro75Ser (c.223C>T)?

AlphaMissense predicts likely benign (score 0.0949) — an in-silico prediction, not a clinical call.

TAF4 p.Pro75Ser

c.223C>T · rs1259961111 · VCV2375608

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0949 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.163%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0949	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -7.57	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 0.84	GERP 0.16, phastCons 0.43
Regional constraint	o/e 1.46	unconstrained · MANE · 1,359 bp · p 3.3e-26 · regional, not allelic
Overall
CADD	13.88	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 0.163% East Asian · 14/8,614 alleles

Filtering AF 0.0982% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0787%

Overall 0.0101% 99/983,266 alleles · rare exomes 66/839,008 · genomes 33/144,258 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.163%	615
Middle Eastern	0.104%	965
South Asian	0.0731%	1,369
Finnishnot grpmax-eligible	0.0563%	1,778
Remaining individualsnot grpmax-eligible	0.0203%	4,934
European (non-Finnish)	0.00662%	15,103
Admixed American	0.00632%	15,828

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: TAF4
Protein: p.Pro75Ser
Coding: c.223C>T
MANE Select: NM_003185
dbSNP: rs1259961111
Type: single nucleotide variant
Location: chr20:62065588 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.71 · 32 PDB
Residue 75: the 'disordered' region

Full TAF4 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

TAF4 p.Pro75Ala Uncertain significance ★ ⚠ same residue
TAF4 p.Ala153Val Uncertain significance ★★ ⚠ same condition
TAF4 p.Ala251Thr Uncertain significance ★★ ⚠ same condition
TAF4 p.Arg774Gln Uncertain significance ★★ ⚠ same condition
TAF4 p.Gly171Cys Uncertain significance ★★ ⚠ same condition
TAF4 p.Gly306Glu Uncertain significance ★★ ⚠ same condition
TAF4 p.Leu58Val Uncertain significance ★★ ⚠ same condition
TAF4 p.Pro241Leu 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/taf4-p-pro75ser (accessed [today's date]).

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