Is TAF1 p.Ala1663Gly (c.4988C>G) pathogenic?

TAF1 p.Ala1663Gly (c.4988C>G) is classified Uncertain significance in TAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-08). AlphaMissense: likely benign (0.0959); Very rare (popmax 0.00175%, sas).

How common is TAF1 p.Ala1663Gly (c.4988C>G) in the general population?

TAF1 p.Ala1663Gly (c.4988C>G) is very rare (popmax 0.00175%, sas) (gnomAD).

What do computational predictors say about TAF1 p.Ala1663Gly (c.4988C>G)?

AlphaMissense predicts likely benign (score 0.0959) — an in-silico prediction, not a clinical call.

TAF1 p.Ala1663Gly

c.4988C>G · VCV4281773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0959 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00175%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0959	likely benign
REVEL	0.109	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 3.3	GERP 1.4, phastCons 0.99
Regional constraint	o/e 0.70	unconstrained · MANE · 5,801 bp · p 9.2e-05 · regional, not allelic
Overall
CADD	18.5	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 A1662G vs ClinVar A1663G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% South Asian · 1/56,983 alleles

Overall 8.25e-05% 1/1,211,547 alleles · very rare exomes 1/1,097,702 · genomes 0/113,845 · 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.Ala1663Gly
Coding: c.4988C>G
MANE Select: NM_004606
Type: single nucleotide variant
Location: chrX:71458290 (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.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
TAF1 c.1774-3T>C Uncertain significance ★★ 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-ala1663gly (accessed [today's date]).

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