Is TAF6 p.Ala447Pro (c.1339G>C) pathogenic?

TAF6 p.Ala447Pro (c.1339G>C) is classified Uncertain significance in TAF6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-28). AlphaMissense: ambiguous (0.5163); Ultra-rare (popmax 0.0117%, amr); Associated with Alazami-Yuan syndrome.

What condition is associated with TAF6 p.Ala447Pro (c.1339G>C)?

TAF6 p.Ala447Pro (c.1339G>C) is associated with Alazami-Yuan syndrome (ClinVar).

How common is TAF6 p.Ala447Pro (c.1339G>C) in the general population?

TAF6 p.Ala447Pro (c.1339G>C) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about TAF6 p.Ala447Pro (c.1339G>C)?

AlphaMissense predicts ambiguous (score 0.5163) — an in-silico prediction, not a clinical call.

TAF6 p.Ala447Pro

c.1339G>C · rs770429821 · VCV3239236

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5163 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Alazami-Yuan syndrome

Computational evidence

Protein change
AlphaMissense	0.5163	ambiguous
REVEL	0.102	moderately benign-leaning
SaProt	LLR -8.59	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,742 bp · p 0.9 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/59,988 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00174% 28/1,613,672 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229
Admixed Americangrpmax	0.0117%	8,570
Remaining individualsnot grpmax-eligible	0.0064%	15,619
European (non-Finnish)	0.000848%	117,978

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala447Pro
Coding: c.1339G>C
MANE Select: NM_004722 · reported on NM_139315
dbSNP: rs770429821
Type: single nucleotide variant
Location: chr7:100108486 (GRCh38)

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

Disease context

Alazami-Yuan syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ala447pro (accessed [today's date]).

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