Is CCRL2 p.Asp339Gly (c.1016A>G) pathogenic?

CCRL2 p.Asp339Gly (c.1016A>G) is classified Uncertain significance in CCRL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: likely benign (0.0766); Rare (popmax 0.112%, eas).

How common is CCRL2 p.Asp339Gly (c.1016A>G) in the general population?

CCRL2 p.Asp339Gly (c.1016A>G) is rare (popmax 0.112%, eas) (gnomAD).

What do computational predictors say about CCRL2 p.Asp339Gly (c.1016A>G)?

AlphaMissense predicts likely benign (score 0.0766) — an in-silico prediction, not a clinical call.

CCRL2 p.Asp339Gly

c.1016A>G · rs184378837 · VCV2409321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0766 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.112%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0766	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -5.40	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 0.18	GERP -2.2
Regional constraint	o/e 1.09	unconstrained · MANE · 1,031 bp · p 0.057 · regional, not allelic
Overall
CADD	1.718	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 0.112% East Asian · 50/44,840 alleles

Filtering AF 0.0868% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0781%

Overall 0.0059% 95/1,611,210 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.112%	897
Middle Eastern	0.0165%	6,052
Remaining individualsnot grpmax-eligible	0.00641%	15,601
Admixed American	0.00334%	29,914
European (non-Finnish)	0.00323%	30,997

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: CCRL2
Protein: p.Asp339Gly
Coding: c.1016A>G
MANE Select: NM_003965
dbSNP: rs184378837
Type: single nucleotide variant
Location: chr3:46409095 (GRCh38)
Gene constraint: LOEUF 1.939 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 77.93
Residue 339: the 'disordered' region

Full CCRL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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/ccrl2-p-asp339gly (accessed [today's date]).

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