Is TAF1 p.Pro299Ser (c.895C>T) pathogenic?

TAF1 p.Pro299Ser (c.895C>T) is classified Uncertain significance in TAF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-28). AlphaMissense: likely benign (0.0797); Very rare (popmax 0.000112%, nfe).

How common is TAF1 p.Pro299Ser (c.895C>T) in the general population?

TAF1 p.Pro299Ser (c.895C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about TAF1 p.Pro299Ser (c.895C>T)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

TAF1 p.Pro299Ser

c.895C>T · rs2520137955 · VCV2501973

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 11 kb · p 7e-27 · regional, not allelic
Overall
CADD	20.4	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 is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P298S vs ClinVar P299S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,162 alleles

Overall 8.26e-05% 1/1,210,760 alleles · very rare exomes 1/1,097,320 · genomes 0/113,440 · 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: TAF1
Protein: p.Pro299Ser
Coding: c.895C>T
MANE Select: NM_004606
dbSNP: rs2520137955
Type: single nucleotide variant
Location: chrX:71377783 (GRCh38)
Structure: AlphaFold pLDDT 62.62 · 65 PDB

Full TAF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TAF1 p.Pro299= Likely benign ★ same residue
TAF1 p.Arg1062Cys Likely pathogenic ★★ ⚠ same type
TAF1 p.Arg1234Gln Pathogenic/Likely pathogenic ★★ same type
TAF1 p.Arg1432His Pathogenic ★★ same type
TAF1 p.Arg870Cys Pathogenic/Likely pathogenic ★★ same type
TAF1 p.Asn1497His Pathogenic/Likely pathogenic ★★ same type
TAF1 p.Ile1317Thr Pathogenic ★★ same type
TAF1 p.Phe403Val Pathogenic/Likely pathogenic ★★ same type

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/taf1-p-pro299ser (accessed [today's date]).

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