Is ABCF1 p.His628Arg (c.1883A>G) pathogenic?

ABCF1 p.His628Arg (c.1883A>G) is classified Uncertain significance in ABCF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-15). AlphaMissense: ambiguous (0.411); Ultra-rare (popmax 0.0102%, nfe).

How common is ABCF1 p.His628Arg (c.1883A>G) in the general population?

ABCF1 p.His628Arg (c.1883A>G) is ultra-rare (popmax 0.0102%, nfe) (gnomAD).

What do computational predictors say about ABCF1 p.His628Arg (c.1883A>G)?

AlphaMissense predicts ambiguous (score 0.411) — an in-silico prediction, not a clinical call.

ABCF1 p.His628Arg

c.1883A>G · rs148962845 · VCV2205761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.411 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0102%, nfe)

Computational evidence

Protein change
AlphaMissense	0.411	ambiguous
REVEL	0.606	indeterminate
SaProt	LLR -14.56	damaging
Splicing
SpliceAI	Δ0.34	donor gain · deltas
Pangolin	Δ0.34	gain · loss 0.09 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 5,079 bp · p 4.6e-11 · regional, not allelic
Overall
CADD	27.1	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 0.0102% European (non-Finnish) · 120/1,175,982 alleles

Filtering AF 0.0087% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00814%

Overall 0.00772% 124/1,606,138 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0102%	9,800
Admixed American	0.00342%	29,267
Remaining individualsnot grpmax-eligible	0.00322%	31,009

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.His628Arg
Coding: c.1883A>G
MANE Select: NM_001025091
dbSNP: rs148962845
Type: single nucleotide variant
Location: chr6:30586303 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.68 · 1 PDB
Residue 628: the abc transporter 2 domain; a β-strand

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

Similar variants

ABCF1 p.Ala117Thr Uncertain significance ★ ⚠ same type
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-his628arg (accessed [today's date]).

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