Is ABCF1 p.Thr449Ile (c.1346C>T) pathogenic?

ABCF1 p.Thr449Ile (c.1346C>T) is classified Uncertain significance in ABCF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely pathogenic (0.8575); Ultra-rare (popmax 0.0446%, eas).

How common is ABCF1 p.Thr449Ile (c.1346C>T) in the general population?

ABCF1 p.Thr449Ile (c.1346C>T) is ultra-rare (popmax 0.0446%, eas) (gnomAD).

What do computational predictors say about ABCF1 p.Thr449Ile (c.1346C>T)?

AlphaMissense predicts likely pathogenic (score 0.8575) — an in-silico prediction, not a clinical call.

ABCF1 p.Thr449Ile

c.1346C>T · rs542422641 · VCV3129353

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8575 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0446%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8575	likely pathogenic
REVEL	0.838	moderately pathogenic-leaning
SaProt	LLR -10.24	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 5.7	phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 2,182 bp · p 7.6e-09 · regional, not allelic
Overall
CADD	29.0	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 0.0446% East Asian · 20/44,862 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00136% 22/1,612,296 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0446%	2,243
Remaining individualsnot grpmax-eligible	0.0016%	62,466
European (non-Finnish)	8.48e-05%	1,179,576

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: ABCF1
Protein: p.Thr449Ile
Coding: c.1346C>T
MANE Select: NM_001025091
dbSNP: rs542422641
Type: single nucleotide variant
Location: chr6:30584521 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.68 · 1 PDB
Residue 449: the abc transporter 1 domain; an α-helix

Full ABCF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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ABCF1 p.Ala194Thr Uncertain significance ★ ⚠ same type
ABCF1 p.Ala221Thr Uncertain significance ★ ⚠ same type
ABCF1 p.Ala251Thr Uncertain significance ★ ⚠ same type
ABCF1 p.Ala276Val Uncertain significance ★ ⚠ same type
ABCF1 p.Ala328Asp Uncertain significance ★ ⚠ same type
ABCF1 p.Ala427Thr Uncertain significance ★ ⚠ same type
ABCF1 p.Ala598Gly 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/abcf1-p-thr449ile (accessed [today's date]).

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