Is ARF1 p.Thr48Ile (c.143C>T) pathogenic?

ARF1 p.Thr48Ile (c.143C>T) is classified Likely pathogenic in ARF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-16). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1; Associated with periventricular nodular heterotopia 8.

What condition is associated with ARF1 p.Thr48Ile (c.143C>T)?

ARF1 p.Thr48Ile (c.143C>T) is associated with periventricular nodular heterotopia 8 (ClinVar).

How common is ARF1 p.Thr48Ile (c.143C>T) in the general population?

ARF1 p.Thr48Ile (c.143C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARF1 p.Thr48Ile (c.143C>T)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

ARF1 p.Thr48Ile

c.143C>T · rs1571844539 · VCV690284

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

periventricular nodular heterotopia 8

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic ✓ concordant with ClinVar · top 8% in ARF1
REVEL	0.966	strongly pathogenic-leaning
SaProt	LLR -12.36	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 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.14	constrained · MANE · 268 bp · p 2.1e-15 · regional, not allelic
Overall
CADD	26.9	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: ARF1
Protein: p.Thr48Ile
Coding: c.143C>T
MANE Select: NM_001658
dbSNP: rs1571844539
Type: single nucleotide variant
Location: chr1:228097257 (GRCh38)
Gene constraint: LOEUF 0.247 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 40 PDB
Residue 48: a β-strand

Full ARF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

periventricular nodular heterotopia 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARF1 p.Arg19Cys Likely pathogenic ★★ same condition
ARF1 p.Arg99His Pathogenic/Likely pathogenic ★★ same condition
ARF1 p.Gly70Ser Likely pathogenic ★★ same condition
ARF1 p.Tyr35Asp Pathogenic/Likely pathogenic ★★ same condition
ARF1 p.Arg99Cys Likely pathogenic ★ same condition
ARF1 p.Lys127Glu Pathogenic ★ same condition
ARF1 p.Phe51Leu Pathogenic ★ same condition
ARF1 p.Pro131Arg Pathogenic ★ same condition

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/arf1-p-thr48ile (accessed [today's date]).

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