Is TG p.Ser1591Phe (c.4772C>T) pathogenic?

TG p.Ser1591Phe (c.4772C>T) is classified Uncertain significance in TG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely benign (0.2603); Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

What condition is associated with TG p.Ser1591Phe (c.4772C>T)?

TG p.Ser1591Phe (c.4772C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TG p.Ser1591Phe (c.4772C>T) in the general population?

TG p.Ser1591Phe (c.4772C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about TG p.Ser1591Phe (c.4772C>T)?

AlphaMissense predicts likely benign (score 0.2603) — an in-silico prediction, not a clinical call.

TG p.Ser1591Phe

c.4772C>T · VCV3968008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2603 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2603	likely benign
REVEL	0.305	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 268 kb · p 0.022 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/59,996 alleles

Filtering AF 0.00588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00541%

Overall 0.00564% 91/1,613,980 alleles · very rare exomes 85/1,461,856 · genomes 6/152,124 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	11,999
European (non-Finnish)	0.00712%	14,048
Remaining individualsnot grpmax-eligible	0.0016%	62,480
African / African-American	0.00134%	74,904

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: TG
Protein: p.Ser1591Phe
Coding: c.4772C>T
MANE Select: NM_003235
Type: single nucleotide variant
Location: chr8:132929148 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)

Full TG 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

TG p.Ser1591= Likely benign ★ same residue
TG p.Ala1033Val Uncertain significance ★★ ⚠ same condition
TG p.Ala1419Glu Uncertain significance ★★ same condition
TG p.Ala1419Val Uncertain significance ★★ ⚠ same condition
TG p.Ala1583Val Uncertain significance ★★ ⚠ same condition
TG p.Ala1631Ser Uncertain significance ★★ ⚠ same condition
TG p.Ala402Gly Uncertain significance ★★ ⚠ same condition
TG p.Ala457Val Uncertain significance ★★ 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/tg-p-ser1591phe (accessed [today's date]).

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