Is ABCF1 p.Arg100Cys (c.298C>T) pathogenic?

ABCF1 p.Arg100Cys (c.298C>T) is classified Uncertain significance in ABCF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). AlphaMissense: likely benign (0.254); Ultra-rare (popmax 0.0339%, nfe).

How common is ABCF1 p.Arg100Cys (c.298C>T) in the general population?

ABCF1 p.Arg100Cys (c.298C>T) is ultra-rare (popmax 0.0339%, nfe) (gnomAD).

What do computational predictors say about ABCF1 p.Arg100Cys (c.298C>T)?

AlphaMissense predicts likely benign (score 0.254) — an in-silico prediction, not a clinical call.

ABCF1 p.Arg100Cys

c.298C>T · rs543085187 · VCV3129391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.254 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0339%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.254	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -10.56	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 12 kb · p 0.96 · regional, not allelic
Overall
CADD	33.0	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 0.0339% European (non-Finnish) · 400/1,179,980 alleles

Filtering AF 0.0311% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.03%

Overall 0.0261% 421/1,613,866 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0339%	2,950
Remaining individualsnot grpmax-eligible	0.016%	6,251
African / African-American	0.0147%	6,811

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.Arg100Cys
Coding: c.298C>T
MANE Select: NM_001025091
dbSNP: rs543085187
Type: single nucleotide variant
Location: chr6:30578157 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.68 · 1 PDB
Residue 100: the 'disordered' region

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-arg100cys (accessed [today's date]).

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