Is ARF1 p.Ala137= (c.411C>T) pathogenic?

ARF1 p.Ala137= (c.411C>T) is classified Likely benign in ARF1 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-07-01). Rare (popmax 0.388%, nfe).

How common is ARF1 p.Ala137= (c.411C>T) in the general population?

ARF1 p.Ala137= (c.411C>T) is rare (popmax 0.388%, nfe) (gnomAD).

ARF1 p.Ala137=

c.411C>T · rs143463838 · VCV2570755

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.388%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -3.7
Overall
CADD	0.303	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.388% European (non-Finnish) · 4,574/1,179,958 alleles

Filtering AF 0.378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.374%

Overall 0.335% 5,404/1,614,060 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.415%	241
Remaining individualsnot grpmax-eligible	0.39%	256
European (non-Finnish)grpmax	0.388%	258
Ashkenazi Jewishnot grpmax-eligible	0.318%	315
Middle Eastern	0.231%	433
Admixed American	0.143%	698
South Asian	0.0736%	1,359
African / African-American	0.0613%	1,631
East Asian	0.029%	3,451

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ARF1
Protein: p.Ala137=
Coding: c.411C>T
MANE Select: NM_001658
dbSNP: rs143463838
Type: single nucleotide variant
Location: chr1:228097878 (GRCh38)
Gene constraint: LOEUF 0.247 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 40 PDB
Residue 137: an α-helix

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

Similar variants

ARF1 p.Arg19Cys Likely pathogenic ★★ same type
ARF1 p.Arg99His Pathogenic/Likely pathogenic ★★ same type
ARF1 p.Gly70Ser Likely pathogenic ★★ same type
ARF1 p.Thr48Ile Likely pathogenic ★★ same type
ARF1 p.Tyr35Asp Pathogenic/Likely pathogenic ★★ same type
ARF1 p.Arg99Cys Likely pathogenic ★ same type
ARF1 p.Lys127Glu Pathogenic ★ same type
ARF1 p.Phe51Leu Pathogenic ★ 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/arf1-p-ala137 (accessed [today's date]).

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