Is ABCF3 p.Arg596Trp (c.1786C>T) pathogenic?

ABCF3 p.Arg596Trp (c.1786C>T) is classified Uncertain significance in ABCF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely benign (0.2792); Ultra-rare (popmax 0.0232%, nfe).

How common is ABCF3 p.Arg596Trp (c.1786C>T) in the general population?

ABCF3 p.Arg596Trp (c.1786C>T) is ultra-rare (popmax 0.0232%, nfe) (gnomAD).

What do computational predictors say about ABCF3 p.Arg596Trp (c.1786C>T)?

AlphaMissense predicts likely benign (score 0.2792) — an in-silico prediction, not a clinical call.

ABCF3 p.Arg596Trp

c.1786C>T · rs751570547 · VCV3129462

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2792 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0232%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2792	likely benign
REVEL	0.751	pathogenic-leaning
SaProt	LLR -10.26	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,487 bp · p 0.0068 · regional, not allelic
Overall
CADD	33.0	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 0.0232% European (non-Finnish) · 267/1,152,440 alleles

Filtering AF 0.0209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0199%

Overall 0.0176% 274/1,555,332 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0232%	4,316
African / African-American	0.00685%	14,603
Remaining individualsnot grpmax-eligible	0.00334%	29,923

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: ABCF3
Protein: p.Arg596Trp
Coding: c.1786C>T
MANE Select: NM_018358
dbSNP: rs751570547
Type: single nucleotide variant
Location: chr3:184193137 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.77
Residue 596: the abc transporter 2 domain

Full ABCF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCF3 p.Ala128Ser Uncertain significance ★ ⚠ same type
ABCF3 p.Ala196Val Uncertain significance ★ ⚠ same type
ABCF3 p.Ala280Thr Uncertain significance ★ ⚠ same type
ABCF3 p.Ala293Thr Uncertain significance ★ ⚠ same type
ABCF3 p.Ala303Gly Uncertain significance ★ ⚠ same type
ABCF3 p.Ala312Gly Uncertain significance ★ ⚠ same type
ABCF3 p.Ala312Thr Uncertain significance ★ ⚠ same type
ABCF3 p.Ala391Thr 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/abcf3-p-arg596trp (accessed [today's date]).

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