Is CALCOCO1 p.Asp319Tyr (c.955G>T) pathogenic?

CALCOCO1 p.Asp319Tyr (c.955G>T) is classified Uncertain significance in CALCOCO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). AlphaMissense: likely benign (0.1298); Very rare (popmax 0.00534%, afr).

How common is CALCOCO1 p.Asp319Tyr (c.955G>T) in the general population?

CALCOCO1 p.Asp319Tyr (c.955G>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CALCOCO1 p.Asp319Tyr (c.955G>T)?

AlphaMissense predicts likely benign (score 0.1298) — an in-silico prediction, not a clinical call.

CALCOCO1 p.Asp319Tyr

c.955G>T · VCV3826898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1298 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1298	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -10.87	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 13 kb · p 9.4e-07 · regional, not allelic
Overall
CADD	26.2	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 0.00534% African / African-American · 4/74,936 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,090 alleles · very rare exomes 0/1,461,886 · genomes 4/152,204 · joint denominator

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.Asp319Tyr
Coding: c.955G>T
MANE Select: NM_020898
Type: single nucleotide variant
Location: chr12:53716310 (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.Asp319Val 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-asp319tyr (accessed [today's date]).

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