Is TAF6 p.Pro441Leu (c.1322C>T) pathogenic?

TAF6 p.Pro441Leu (c.1322C>T) is classified Uncertain significance in TAF6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-04). AlphaMissense: likely benign (0.067); Ultra-rare (popmax 0.016%, nfe).

How common is TAF6 p.Pro441Leu (c.1322C>T) in the general population?

TAF6 p.Pro441Leu (c.1322C>T) is ultra-rare (popmax 0.016%, nfe) (gnomAD).

What do computational predictors say about TAF6 p.Pro441Leu (c.1322C>T)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

TAF6 p.Pro441Leu

c.1322C>T · VCV4752017

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -6.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,742 bp · p 0.9 · regional, not allelic
Overall
CADD	21.9	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 0.016% European (non-Finnish) · 189/1,179,464 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0134%

Overall 0.012% 193/1,613,270 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.016%	6,241
Remaining individualsnot grpmax-eligible	0.0032%	31,228
South Asian	0.0022%	45,534

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: TAF6
Protein: p.Pro441Leu
Coding: c.1322C>T
MANE Select: NM_004722 · reported on NM_139315
Type: single nucleotide variant
Location: chr7:100108503 (GRCh38)

Full TAF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/taf6-p-pro441leu (accessed [today's date]).

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