Is ABITRAM p.Arg87Trp (c.259C>T) pathogenic?

ABITRAM p.Arg87Trp (c.259C>T) is classified Uncertain significance in ABITRAM (ClinVar, Single submitter, 2 submitters; last evaluated 2025-06-02). AlphaMissense: likely pathogenic (0.884); Ultra-rare (popmax 0.0369%, amr).

How common is ABITRAM p.Arg87Trp (c.259C>T) in the general population?

ABITRAM p.Arg87Trp (c.259C>T) is ultra-rare (popmax 0.0369%, amr) (gnomAD).

What do computational predictors say about ABITRAM p.Arg87Trp (c.259C>T)?

AlphaMissense predicts likely pathogenic (score 0.884) — an in-silico prediction, not a clinical call.

ABITRAM p.Arg87Trp

c.259C>T · rs150725760 · VCV2529889

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.884 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0369%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.884	likely pathogenic
REVEL	0.243	benign-leaning
SaProt	LLR -12.55	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Pangolin	Δ0.25	loss · gain 0.07 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 3.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 5,196 bp · p 0.73 · regional, not allelic
Overall
CADD	32.0	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 0.0369% Admixed American · 22/59,666 alleles

Filtering AF 0.0304% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.0275% 444/1,612,538 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0369%	2,712
European (non-Finnish)	0.0332%	3,009
Remaining individualsnot grpmax-eligible	0.0176%	5,673
African / African-American	0.0147%	6,805
Finnishnot grpmax-eligible	0.00782%	12,789
East Asian	0.00223%	44,830
South Asian	0.0022%	45,469

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: ABITRAM
Protein: p.Arg87Trp
Coding: c.259C>T
MANE Select: NM_017832
dbSNP: rs150725760
Type: single nucleotide variant
Location: chr9:108936435 (GRCh38)
Gene constraint: LOEUF 1.175 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.21

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

Similar variants

ABITRAM p.Arg87Gln Uncertain significance ★ ⚠ same residue
ABITRAM p.Ala2Val Uncertain significance ★ ⚠ same type
ABITRAM p.Arg173His Uncertain significance ★ ⚠ same type
ABITRAM p.Arg22His Uncertain significance ★ ⚠ same type
ABITRAM p.Gln163Arg Uncertain significance ★ ⚠ same type
ABITRAM p.Gly106Asp Uncertain significance ★ ⚠ same type
ABITRAM p.Gly141Val Uncertain significance ★ ⚠ same type
ABITRAM p.Gly88Glu 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/abitram-p-arg87trp (accessed [today's date]).

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