Is ABCF3 p.Arg580Cys (c.1738C>T) pathogenic?

ABCF3 p.Arg580Cys (c.1738C>T) is classified Uncertain significance in ABCF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: likely benign (0.1001); Ultra-rare (popmax 0.0223%, eas).

How common is ABCF3 p.Arg580Cys (c.1738C>T) in the general population?

ABCF3 p.Arg580Cys (c.1738C>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about ABCF3 p.Arg580Cys (c.1738C>T)?

AlphaMissense predicts likely benign (score 0.1001) — an in-silico prediction, not a clinical call.

ABCF3 p.Arg580Cys

c.1738C>T · VCV4142567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1001 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1001	likely benign
REVEL	0.667	pathogenic-leaning
SaProt	LLR -10.47	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.76 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,487 bp · p 0.0068 · 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 0.0223% East Asian · 10/44,906 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.0013% 21/1,613,912 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,491
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,476
Finnishnot grpmax-eligible	0.00156%	64,026
South Asian	0.0011%	91,076
European (non-Finnish)	0.000593%	168,564

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.Arg580Cys
Coding: c.1738C>T
MANE Select: NM_018358
Type: single nucleotide variant
Location: chr3:184192884 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.77
Residue 580: 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-arg580cys (accessed [today's date]).

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