Is ARL3 p.Arg151Ter (c.451C>T) pathogenic?

ARL3 p.Arg151Ter (c.451C>T) is classified Uncertain significance in ARL3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-02-23). Very rare (popmax 0.00144%, nfe).

How common is ARL3 p.Arg151Ter (c.451C>T) in the general population?

ARL3 p.Arg151Ter (c.451C>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

ARL3 p.Arg151Ter

c.451C>T · rs1177720492 · VCV1042524

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (5 of 6, 50 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.51, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,179,998 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00124% 20/1,613,940 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)grpmax	0.00144%	69,412
African / African-American	0.00133%	74,912
South Asian	0.0011%	91,066

Remaining individuals 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: ARL3
Protein: p.Arg151Ter
Coding: c.451C>T
MANE Select: NM_004311
dbSNP: rs1177720492
Type: single nucleotide variant
Location: chr10:102685866 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 92.73

Full ARL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARL3 p.Arg151Gln Uncertain significance ★★ ⚠ same residue
ARL3 p.Arg151= Likely benign ★ same residue
ARL3 p.Gly70Glu Pathogenic/Likely pathogenic ★★ same type
ARL3 c.3+1G>A Uncertain significance ★★ same type
ARL3 c.3+2T>C Uncertain significance ★★ same type
ARL3 c.3+3G>T Uncertain significance ★★ same type
ARL3 c.316-2A>G Uncertain significance ★★ same type
ARL3 p.Ala13Ser 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/arl3-p-arg151ter (accessed [today's date]).

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