Is CLSTN3 p.Arg779Gln (c.2336G>A) pathogenic?

CLSTN3 p.Arg779Gln (c.2336G>A) is classified Uncertain significance in CLSTN3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.1089); Ultra-rare (popmax 0.0164%, mid).

How common is CLSTN3 p.Arg779Gln (c.2336G>A) in the general population?

CLSTN3 p.Arg779Gln (c.2336G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CLSTN3 p.Arg779Gln (c.2336G>A)?

AlphaMissense predicts likely benign (score 0.1089) — an in-silico prediction, not a clinical call.

CLSTN3 p.Arg779Gln

c.2336G>A · VCV3267894

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1089 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1089	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -7.29	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 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 27 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	27.3	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000805% 13/1,614,052 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
East Asian	0.00891%	11,223
African / African-American	0.00267%	37,466
South Asian	0.0022%	45,544
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000254%	393,340

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: CLSTN3
Protein: p.Arg779Gln
Coding: c.2336G>A
MANE Select: NM_014718
Type: single nucleotide variant
Location: chr12:7150634 (GRCh38)
Gene constraint: LOEUF 0.508 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 77.80

Full CLSTN3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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CLSTN3 p.Ala153Thr Uncertain significance ★ ⚠ same type
CLSTN3 p.Ala304Val Uncertain significance ★ ⚠ same type
CLSTN3 p.Ala312Pro Uncertain significance ★ ⚠ same type
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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/clstn3-p-arg779gln (accessed [today's date]).

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