Is AGTRAP p.Arg130Cys (c.388C>T) pathogenic?

AGTRAP p.Arg130Cys (c.388C>T) is classified Uncertain significance in AGTRAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.1131); Ultra-rare (popmax 0.0164%, mid).

How common is AGTRAP p.Arg130Cys (c.388C>T) in the general population?

AGTRAP p.Arg130Cys (c.388C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about AGTRAP p.Arg130Cys (c.388C>T)?

AlphaMissense predicts likely benign (score 0.1131) — an in-silico prediction, not a clinical call.

AGTRAP p.Arg130Cys

c.388C>T · rs142297789 · VCV2410670

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1131 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1131	likely benign
REVEL	0.283	benign-leaning
SaProt	LLR -11.19	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 0.52
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.071 · regional, not allelic
Overall
CADD	27.3	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00502% 81/1,613,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
European (non-Finnish)	0.0061%	16,389
South Asian	0.00329%	30,359
Remaining individualsnot grpmax-eligible	0.0032%	31,239
African / African-American	0.00267%	37,445
Admixed American	0.00167%	59,982

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: AGTRAP
Protein: p.Arg130Cys
Coding: c.388C>T
MANE Select: NM_020350
dbSNP: rs142297789
Type: single nucleotide variant
Location: chr1:11750100 (GRCh38)
Gene constraint: LOEUF 0.838 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 80.97

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

Similar variants

AGTRAP p.Arg130Ser Uncertain significance ★ ⚠ same residue
AGTRAP p.Arg157Gln Likely benign ★★ same type
AGTRAP p.Ala53Thr Uncertain significance ★ ⚠ same type
AGTRAP p.Arg113Cys Uncertain significance ★ ⚠ same type
AGTRAP p.Arg113His Uncertain significance ★ ⚠ same type
AGTRAP p.Arg157Leu Uncertain significance ★ ⚠ same type
AGTRAP p.Arg48Gln Uncertain significance ★ ⚠ same type
AGTRAP p.Arg48Trp 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/agtrap-p-arg130cys (accessed [today's date]).

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