Is ARL3 p.Ser55Asn (c.164G>A) pathogenic?

ARL3 p.Ser55Asn (c.164G>A) is classified Uncertain significance in ARL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). AlphaMissense: ambiguous (0.5139); Ultra-rare (popmax 0.0169%, amr).

How common is ARL3 p.Ser55Asn (c.164G>A) in the general population?

ARL3 p.Ser55Asn (c.164G>A) is ultra-rare (popmax 0.0169%, amr) (gnomAD).

What do computational predictors say about ARL3 p.Ser55Asn (c.164G>A)?

AlphaMissense predicts ambiguous (score 0.5139) — an in-silico prediction, not a clinical call.

ARL3 p.Ser55Asn

c.164G>A · rs1159431863 · VCV2074794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5139 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5139	ambiguous
REVEL	0.287	benign-leaning
SaProt	LLR -10.82	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 37 kb · p 8.6e-05 · regional, not allelic
Overall
CADD	25.6	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 0.0169% Admixed American · 10/59,310 alleles

Filtering AF 0.0091% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00688%

Overall 0.000747% 12/1,606,282 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0169%	5,931
East Asian	0.00447%	22,376

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.Ser55Asn
Coding: c.164G>A
MANE Select: NM_004311
dbSNP: rs1159431863
Type: single nucleotide variant
Location: chr10:102699473 (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.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
ARL3 p.Ala140Val Uncertain significance ★★ ⚠ same type
ARL3 p.Ala179Pro 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-ser55asn (accessed [today's date]).

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