Is CALCOCO1 p.Arg384Ser (c.1150C>A) pathogenic?

CALCOCO1 p.Arg384Ser (c.1150C>A) is classified Uncertain significance in CALCOCO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: likely pathogenic (0.8977); Very rare (popmax 0.00833%, amr).

How common is CALCOCO1 p.Arg384Ser (c.1150C>A) in the general population?

CALCOCO1 p.Arg384Ser (c.1150C>A) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CALCOCO1 p.Arg384Ser (c.1150C>A)?

AlphaMissense predicts likely pathogenic (score 0.8977) — an in-silico prediction, not a clinical call.

CALCOCO1 p.Arg384Ser

c.1150C>A · VCV3826896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8977 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8977	likely pathogenic · top 9% in CALCOCO1
REVEL	0.302	indeterminate
SaProt	LLR -7.74	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 13 kb · p 9.4e-07 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,006 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000434% 7/1,614,094 alleles · very rare exomes 5/1,461,876 · genomes 2/152,218 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,001
European (non-Finnish)	0.000169%	590,023

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: CALCOCO1
Protein: p.Arg384Ser
Coding: c.1150C>A
MANE Select: NM_020898
Type: single nucleotide variant
Location: chr12:53715903 (GRCh38)
Gene constraint: LOEUF 0.629 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.57

Full CALCOCO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CALCOCO1 p.Arg384His Uncertain significance ★ ⚠ same residue
CALCOCO1 p.Gln112Lys Uncertain significance ★★ ⚠ same type
CALCOCO1 p.Ala303Thr Uncertain significance ★ ⚠ same type
CALCOCO1 p.Ala303Val Uncertain significance ★ ⚠ same type
CALCOCO1 p.Ala322Val Uncertain significance ★ ⚠ same type
CALCOCO1 p.Ala369Thr Uncertain significance ★ ⚠ same type
CALCOCO1 p.Ala395Thr Uncertain significance ★ ⚠ same type
CALCOCO1 p.Ala478Asp 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/calcoco1-p-arg384ser (accessed [today's date]).

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