Is ABCF1 p.Ile775Val (c.2323A>G) pathogenic?

ABCF1 p.Ile775Val (c.2323A>G) is classified Uncertain significance in ABCF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-28). AlphaMissense: ambiguous (0.4822); Ultra-rare (popmax 0.016%, afr).

How common is ABCF1 p.Ile775Val (c.2323A>G) in the general population?

ABCF1 p.Ile775Val (c.2323A>G) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about ABCF1 p.Ile775Val (c.2323A>G)?

AlphaMissense predicts ambiguous (score 0.4822) — an in-silico prediction, not a clinical call.

ABCF1 p.Ile775Val

c.2323A>G · VCV3409272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4822 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4822	ambiguous
REVEL	0.27	benign-leaning
SaProt	LLR -8.89	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	24.1	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 0.016% African / African-American · 12/74,886 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.000993% 16/1,611,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,240
East Asian	0.00446%	22,439
Admixed American	0.00167%	59,924
South Asian	0.0011%	90,988

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.Ile775Val
Coding: c.2323A>G
MANE Select: NM_001025091
Type: single nucleotide variant
Location: chr6:30590330 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.68 · 1 PDB
Residue 775: 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-ile775val (accessed [today's date]).

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