Is TAF4 p.Pro274Arg (c.821C>G) pathogenic?

TAF4 p.Pro274Arg (c.821C>G) is classified Uncertain significance in TAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely benign (0.1534); No allele count reported in gnomAD v4.1 (AN 274,034); Associated with Inborn genetic diseases.

What condition is associated with TAF4 p.Pro274Arg (c.821C>G)?

TAF4 p.Pro274Arg (c.821C>G) is associated with Inborn genetic diseases (ClinVar).

How common is TAF4 p.Pro274Arg (c.821C>G) in the general population?

TAF4 p.Pro274Arg (c.821C>G) is no allele count reported in gnomAD v4.1 (AN 274,034) (gnomAD).

What do computational predictors say about TAF4 p.Pro274Arg (c.821C>G)?

AlphaMissense predicts likely benign (score 0.1534) — an in-silico prediction, not a clinical call.

TAF4 p.Pro274Arg

c.821C>G · VCV4632595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1534 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 274,034)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1534	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -8.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.6	GERP 0.17, phastCons 1
Regional constraint	o/e 1.46	unconstrained · MANE · 1,359 bp · p 3.3e-26 · regional, not allelic
Overall
CADD	15.68	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

No allele count reported in gnomAD v4.1 (AN 274,034). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TAF4
Protein: p.Pro274Arg
Coding: c.821C>G
MANE Select: NM_003185
Type: single nucleotide variant
Location: chr20:62064990 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.71 · 32 PDB
Residue 274: 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.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
TAF4 p.Asn220Ser Likely benign ★★ 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-pro274arg (accessed [today's date]).

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