Is ARL6IP4 c.287C>T pathogenic?

ARL6IP4 c.287C>T is classified Uncertain significance in ARL6IP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: likely benign (0.1348); Very rare (popmax 0.0031%, eas).

How common is ARL6IP4 c.287C>T in the general population?

ARL6IP4 c.287C>T is very rare (popmax 0.0031%, eas) (gnomAD).

What do computational predictors say about ARL6IP4 c.287C>T?

AlphaMissense predicts likely benign (score 0.1348) — an in-silico prediction, not a clinical call.

ARL6IP4 c.287C>T

rs973346304 · VCV2596536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1348 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0031%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1348	likely benign
REVEL	0.03	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.14	GERP -1.1, phastCons 0.24
Overall
CADD	20.5	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0031% East Asian · 1/32,296 alleles

Filtering AF 0.000508% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00019%

Overall 0.000369% 5/1,353,300 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0031%	32,296
African / African-American	0.00306%	32,656
European (non-Finnish)	0.000189%	529,182

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: ARL6IP4
Coding: c.287C>T
MANE Select: NM_018694
dbSNP: rs973346304
Type: single nucleotide variant
Location: chr12:122980674 (GRCh38)
Gene constraint: LOEUF 1.277 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.86

Full ARL6IP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARL6IP4 c.103G>T Uncertain significance ★ ⚠ same type
ARL6IP4 c.136A>G Uncertain significance ★ ⚠ same type
ARL6IP4 c.164G>A Uncertain significance ★ ⚠ same type
ARL6IP4 c.167C>G Uncertain significance ★ ⚠ same type
ARL6IP4 c.191G>C Uncertain significance ★ ⚠ same type
ARL6IP4 c.203C>G Uncertain significance ★ ⚠ same type
ARL6IP4 c.205C>G Uncertain significance ★ ⚠ same type
ARL6IP4 c.210C>G 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/arl6ip4-c-287c-t (accessed [today's date]).

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