Is ARL16 p.Ala7Pro (c.19G>C) pathogenic?

ARL16 p.Ala7Pro (c.19G>C) is classified Uncertain significance in ARL16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: likely benign (0.2218); Very rare (popmax 8.48e-05%, nfe).

How common is ARL16 p.Ala7Pro (c.19G>C) in the general population?

ARL16 p.Ala7Pro (c.19G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ARL16 p.Ala7Pro (c.19G>C)?

AlphaMissense predicts likely benign (score 0.2218) — an in-silico prediction, not a clinical call.

ARL16 p.Ala7Pro

c.19G>C · VCV3315041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2218 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2218	likely benign
REVEL	0.229	benign-leaning
SaProt	LLR -5.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.059	GERP -3.9, phastCons 0.002
Regional constraint	o/e 1.12	unconstrained · MANE · 2,042 bp · p 0.081 · regional, not allelic
Overall
CADD	8.409	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A31P vs ClinVar A7P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,668 alleles

Overall 0.000137% 2/1,455,504 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,284
European (non-Finnish)grpmax	8.48e-05%	1,178,668

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: ARL16
Protein: p.Ala7Pro
Coding: c.19G>C
MANE Select: NM_001040025
Type: single nucleotide variant
Location: chr17:81683735 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.91
Residue 7: a binding site

Full ARL16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARL16 c.-41G>T Likely pathogenic ★ ⚠ same type
ARL16 c.-20C>A Uncertain significance ★ ⚠ same type
ARL16 c.-3G>A Uncertain significance ★ ⚠ same type
ARL16 p.Ala108Gly Uncertain significance ★ ⚠ same type
ARL16 p.Ala152Thr Uncertain significance ★ ⚠ same type
ARL16 p.Ala167Val Uncertain significance ★ ⚠ same type
ARL16 p.Arg153Cys Uncertain significance ★ ⚠ same type
ARL16 p.Arg57Trp 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/arl16-p-ala7pro (accessed [today's date]).

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