Is TAF4 p.Pro229Ser (c.685C>T) pathogenic?

TAF4 p.Pro229Ser (c.685C>T) is classified Uncertain significance in TAF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-18). AlphaMissense: likely benign (0.0934); Very rare (popmax 0.00154%, sas).

How common is TAF4 p.Pro229Ser (c.685C>T) in the general population?

TAF4 p.Pro229Ser (c.685C>T) is very rare (popmax 0.00154%, sas) (gnomAD).

What do computational predictors say about TAF4 p.Pro229Ser (c.685C>T)?

AlphaMissense predicts likely benign (score 0.0934) — an in-silico prediction, not a clinical call.

TAF4 p.Pro229Ser

c.685C>T · VCV3366735

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0934 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00154%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0934	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -6.76	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 0.3	GERP 0.18, phastCons 1
Regional constraint	o/e 1.46	unconstrained · MANE · 1,359 bp · p 3.3e-26 · regional, not allelic
Overall
CADD	13.49	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 0.00154% South Asian · 1/64,844 alleles

Filtering AF 8.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.4e-05%

Overall 0.000344% 4/1,162,498 alleles · very rare exomes 4/1,021,112 · genomes 0/141,386 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00154%	64,844
European (non-Finnish)	0.000325%	307,459

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.Pro229Ser
Coding: c.685C>T
MANE Select: NM_003185
Type: single nucleotide variant
Location: chr20:62065126 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.71 · 32 PDB

Full TAF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TAF4 p.Ala153Val Uncertain significance ★★ ⚠ same type
TAF4 p.Ala251Thr Uncertain significance ★★ ⚠ same type
TAF4 p.Arg774Gln Uncertain significance ★★ ⚠ same type
TAF4 p.Gly171Cys Uncertain significance ★★ ⚠ same type
TAF4 p.Gly306Glu Uncertain significance ★★ ⚠ same type
TAF4 p.Leu58Val Uncertain significance ★★ ⚠ same type
TAF4 p.Pro241Leu Uncertain significance ★★ ⚠ same type
TAF4 p.Asn220Ser Likely benign ★★ 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/taf4-p-pro229ser (accessed [today's date]).

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