Is ABCF3 p.Arg384Cys (c.1150C>T) pathogenic?

ABCF3 p.Arg384Cys (c.1150C>T) is classified Uncertain significance in ABCF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: ambiguous (0.4718); Ultra-rare (popmax 0.0164%, mid).

How common is ABCF3 p.Arg384Cys (c.1150C>T) in the general population?

ABCF3 p.Arg384Cys (c.1150C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about ABCF3 p.Arg384Cys (c.1150C>T)?

AlphaMissense predicts ambiguous (score 0.4718) — an in-silico prediction, not a clinical call.

ABCF3 p.Arg384Cys

c.1150C>T · VCV3883166

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4718 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4718	ambiguous
REVEL	0.882	moderately pathogenic-leaning
SaProt	LLR -10.29	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.53 · 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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000434% 7/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.0011%	91,082
European (non-Finnish)	0.000424%	236,010

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.Arg384Cys
Coding: c.1150C>T
MANE Select: NM_018358
Type: single nucleotide variant
Location: chr3:184189593 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.77
Residue 384: the abc transporter 1 domain

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

Similar variants

ABCF3 p.Arg384His Uncertain significance ★ ⚠ same residue
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

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-arg384cys (accessed [today's date]).

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