Is ABCF3 p.Arg419Trp (c.1255C>T) pathogenic?

ABCF3 p.Arg419Trp (c.1255C>T) is classified Uncertain significance in ABCF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-31). AlphaMissense: likely pathogenic (0.613); Very rare (popmax 0.0033%, nfe).

How common is ABCF3 p.Arg419Trp (c.1255C>T) in the general population?

ABCF3 p.Arg419Trp (c.1255C>T) is very rare (popmax 0.0033%, nfe) (gnomAD).

What do computational predictors say about ABCF3 p.Arg419Trp (c.1255C>T)?

AlphaMissense predicts likely pathogenic (score 0.613) — an in-silico prediction, not a clinical call.

ABCF3 p.Arg419Trp

c.1255C>T · VCV3882460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.613	likely pathogenic
REVEL	0.899	moderately pathogenic-leaning
SaProt	LLR -14.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,487 bp · p 0.0068 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% European (non-Finnish) · 39/1,180,030 alleles

Filtering AF 0.00247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00273% 44/1,613,982 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0033%	30,257
Remaining individualsnot grpmax-eligible	0.0032%	31,243
East Asian	0.00223%	44,896
Finnishnot grpmax-eligible	0.00156%	63,958
South Asian	0.0011%	91,088

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.Arg419Trp
Coding: c.1255C>T
MANE Select: NM_018358
Type: single nucleotide variant
Location: chr3:184189698 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.77
Residue 419: the abc transporter 1 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-arg419trp (accessed [today's date]).

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