Is GOT1 p.Arg86Cys (c.256C>T) pathogenic?

GOT1 p.Arg86Cys (c.256C>T) is classified Uncertain significance in GOT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely benign (0.1367); Very rare (popmax 0.00934%, afr).

How common is GOT1 p.Arg86Cys (c.256C>T) in the general population?

GOT1 p.Arg86Cys (c.256C>T) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about GOT1 p.Arg86Cys (c.256C>T)?

AlphaMissense predicts likely benign (score 0.1367) — an in-silico prediction, not a clinical call.

GOT1 p.Arg86Cys

c.256C>T · rs754787823 · VCV2455073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1367 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1367	likely benign
REVEL	0.484	indeterminate
SaProt	LLR -13.75	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -1.2, phastCons 1
Overall
CADD	22.1	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 0.00934% African / African-American · 7/74,910 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00118% 19/1,613,904 alleles · very rare exomes 12/1,461,752 · genomes 7/152,152 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,701
South Asian	0.0011%	91,074
European (non-Finnish)	0.000932%	107,269

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: GOT1
Protein: p.Arg86Cys
Coding: c.256C>T
MANE Select: NM_002079
dbSNP: rs754787823
Type: single nucleotide variant
Location: chr10:99420668 (GRCh38)
Structure: AlphaFold pLDDT 88.17

Full GOT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GOT1 p.Arg86His Uncertain significance ★ ⚠ same residue
GOT1 c.643-5C>T Benign/Likely benign ★★ same type
GOT1 p.Glu183Gly Benign ★★ ⚠ same type
GOLT1B p.Gly100Asp Uncertain significance ★ ⚠ same type
GOLT1B p.Gly132Ala Uncertain significance ★ ⚠ same type
GOLT1B p.Leu41Ile Uncertain significance ★ ⚠ same type
GOLT1B p.Lys64Asn Uncertain significance ★ ⚠ same type
GOLT1B p.Phe56Cys 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/got1-p-arg86cys (accessed [today's date]).

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