Is TST p.Ser77Arg (c.231C>G) pathogenic?

TST p.Ser77Arg (c.231C>G) is classified Uncertain significance in TST (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-26). AlphaMissense: ambiguous (0.4837); Ultra-rare (popmax 0.0673%, eas).

How common is TST p.Ser77Arg (c.231C>G) in the general population?

TST p.Ser77Arg (c.231C>G) is ultra-rare (popmax 0.0673%, eas) (gnomAD).

What do computational predictors say about TST p.Ser77Arg (c.231C>G)?

AlphaMissense predicts ambiguous (score 0.4837) — an in-silico prediction, not a clinical call.

TST p.Ser77Arg

c.231C>G · rs781611380 · VCV3183990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4837 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0673%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4837	ambiguous
REVEL	0.236	benign-leaning
SaProt	LLR -9.76	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -0.56, phastCons 0.086
Regional constraint	o/e 0.97	unconstrained · MANE · 7,702 bp · p 0.51 · regional, not allelic
Overall
CADD	18.97	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 0.0673% East Asian · 30/44,606 alleles

Filtering AF 0.0484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0419%

Overall 0.00193% 31/1,605,656 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0673%	1,487
Remaining individualsnot grpmax-eligible	0.00161%	62,126

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: TST
Protein: p.Ser77Arg
Coding: c.231C>G
MANE Select: NM_003312
dbSNP: rs781611380
Type: single nucleotide variant
Location: chr22:37018502 (GRCh38)
Gene constraint: LOEUF 1.478 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.50 · 1 PDB
Residue 77: the rhodanese 1 domain

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

Similar variants

TST p.Arg132Trp Uncertain significance ★ ⚠ same type
TST p.Arg183Ser Uncertain significance ★ ⚠ same type
TST p.Arg187Leu Uncertain significance ★ ⚠ same type
TST p.Arg206His Uncertain significance ★ ⚠ same type
TST p.Arg230Cys Uncertain significance ★ ⚠ same type
TST p.Arg230His Uncertain significance ★ ⚠ same type
TST p.Arg249Cys Uncertain significance ★ ⚠ same type
TST p.Arg282Gln 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/tst-p-ser77arg (accessed [today's date]).

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