Is PLOD2 p.Asp585Val (c.1754A>T) pathogenic?

PLOD2 p.Asp585Val (c.1754A>T) is classified Likely pathogenic in PLOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: likely pathogenic (0.9966); Absent from gnomAD v4.1; Associated with Bruck syndrome 2.

What condition is associated with PLOD2 p.Asp585Val (c.1754A>T)?

PLOD2 p.Asp585Val (c.1754A>T) is associated with Bruck syndrome 2 (ClinVar).

How common is PLOD2 p.Asp585Val (c.1754A>T) in the general population?

PLOD2 p.Asp585Val (c.1754A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLOD2 p.Asp585Val (c.1754A>T)?

AlphaMissense predicts likely pathogenic (score 0.9966) — an in-silico prediction, not a clinical call.

PLOD2 p.Asp585Val

c.1754A>T · VCV3363157

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9966 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bruck syndrome 2

Computational evidence

Protein change
AlphaMissense	0.9966	likely pathogenic ✓ concordant with ClinVar · top 4% in PLOD2
REVEL	0.948	strongly pathogenic-leaning
SaProt	LLR -17.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 90 kb · p 0.85 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D564V vs ClinVar D585V) — verify the residue.

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: PLOD2
Protein: p.Asp585Val
Coding: c.1754A>T
MANE Select: NM_182943
Type: single nucleotide variant
Location: chr3:146072655 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.63
Residue 585: a UniProt-annotated variant site (in brks2; likely pathogenic)

Full PLOD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bruck syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLOD2 p.Asp585Tyr Uncertain significance ★ ⚠ same residue
PLOD2 p.Arg440Ter Pathogenic/Likely pathogenic ★★ same condition
PLOD2 p.Arg495Ter Pathogenic/Likely pathogenic ★★ same condition
PLOD2 p.Arg680Ter Pathogenic/Likely pathogenic ★★ same condition
PLOD2 c.-170C>G Uncertain significance ★★ same condition
PLOD2 p.Ala415Val Uncertain significance ★★ ⚠ same condition
PLOD2 p.Arg619Cys Uncertain significance ★★ ⚠ same condition
PLOD2 p.Arg648Trp Uncertain significance ★★ ⚠ same condition

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/plod2-p-asp585val (accessed [today's date]).

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