Is COASY p.Asp387Tyr (c.1159G>T) pathogenic?

COASY p.Asp387Tyr (c.1159G>T) is classified Uncertain significance in COASY (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-16). AlphaMissense: ambiguous (0.5013); Very rare (popmax 0.00137%, afr).

How common is COASY p.Asp387Tyr (c.1159G>T) in the general population?

COASY p.Asp387Tyr (c.1159G>T) is very rare (popmax 0.00137%, afr) (gnomAD).

What do computational predictors say about COASY p.Asp387Tyr (c.1159G>T)?

AlphaMissense predicts ambiguous (score 0.5013) — an in-silico prediction, not a clinical call.

COASY p.Asp387Tyr

c.1159G>T · VCV3268413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5013 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00137%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5013	ambiguous
REVEL	0.839	moderately pathogenic-leaning
SaProt	LLR -13.63	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.26	acceptor gain · deltas
Pangolin	Δ0.38	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 8.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 3,342 bp · p 0.88 · regional, not allelic
Overall
CADD	32.0	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 0.00137% African / African-American · 1/72,738 alleles

Filtering AF 0.000297% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000215%

Overall 0.00064% 10/1,563,614 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00166%	60,192
African / African-Americangrpmax	0.00137%	72,738
European (non-Finnish)	0.00069%	144,858

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: COASY
Protein: p.Asp387Tyr
Coding: c.1159G>T
MANE Select: NM_025233
Type: single nucleotide variant
Location: chr17:42564820 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.51
Residue 387: the dpck domain; a UniProt-annotated variant site (in nbia6; reduced protein abundance)

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

Similar variants

COASY c.1486-3C>G Pathogenic/Likely pathogenic ★★ same type
COASY p.Ala214Val Likely pathogenic ★★ ⚠ same type
COASY p.Arg377Ter Pathogenic/Likely pathogenic ★★ same type
COASY p.Arg499Cys Pathogenic ★★ same type
COASY p.Gln523Ter Pathogenic ★★ same type
COASY p.Ala206Ser Uncertain significance ★★ ⚠ same type
COASY p.Ala311Val Uncertain significance ★★ ⚠ same type
COASY p.Ala395Thr 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/coasy-p-asp387tyr (accessed [today's date]).

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