Is ABCF1 p.Glu709Asp (c.2127G>C) pathogenic?

ABCF1 p.Glu709Asp (c.2127G>C) is classified Uncertain significance in ABCF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely benign (0.3395); Absent from gnomAD v4.1.

How common is ABCF1 p.Glu709Asp (c.2127G>C) in the general population?

ABCF1 p.Glu709Asp (c.2127G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCF1 p.Glu709Asp (c.2127G>C)?

AlphaMissense predicts likely benign (score 0.3395) — an in-silico prediction, not a clinical call.

ABCF1 p.Glu709Asp

c.2127G>C · VCV4636250

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3395 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3395	likely benign
REVEL	0.74	pathogenic-leaning
SaProt	LLR -8.90	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.57	phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 5,079 bp · p 4.6e-11 · regional, not allelic
Overall
CADD	22.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCF1
Protein: p.Glu709Asp
Coding: c.2127G>C
MANE Select: NM_001025091
Type: single nucleotide variant
Location: chr6:30589868 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.68 · 1 PDB
Residue 709: the abc transporter 2 domain; an α-helix

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-glu709asp (accessed [today's date]).

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