Is COG3 p.Arg38Lys (c.113G>A) pathogenic?

COG3 p.Arg38Lys (c.113G>A) is classified Uncertain significance in COG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: likely benign (0.0855); Absent from gnomAD v4.1.

How common is COG3 p.Arg38Lys (c.113G>A) in the general population?

COG3 p.Arg38Lys (c.113G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COG3 p.Arg38Lys (c.113G>A)?

AlphaMissense predicts likely benign (score 0.0855) — an in-silico prediction, not a clinical call.

COG3 p.Arg38Lys

c.113G>A · VCV3268470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0855 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0855	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.79	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 5.7	GERP 0.76, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 27 kb · p 0.75 · regional, not allelic
Overall
CADD	19.71	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COG3
Protein: p.Arg38Lys
Coding: c.113G>A
MANE Select: NM_031431
Type: single nucleotide variant
Location: chr13:45465149 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.82

Full COG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COG3 p.Ala14Val Uncertain significance ★ ⚠ same type
COG3 p.Ala190Gly Uncertain significance ★ ⚠ same type
COG3 p.Ala227Asp Uncertain significance ★ ⚠ same type
COG3 p.Ala227Thr Uncertain significance ★ ⚠ same type
COG3 p.Ala2Val Uncertain significance ★ ⚠ same type
COG3 p.Ala302Gly Uncertain significance ★ ⚠ same type
COG3 p.Ala364Ser Uncertain significance ★ ⚠ same type
COG3 p.Ala482Val 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/cog3-p-arg38lys (accessed [today's date]).

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