Is PLOD2 p.Ala660Val (c.1979C>T) pathogenic?

PLOD2 p.Ala660Val (c.1979C>T) is classified Uncertain significance in PLOD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.3028); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PLOD2 p.Ala660Val (c.1979C>T)?

PLOD2 p.Ala660Val (c.1979C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PLOD2 p.Ala660Val (c.1979C>T) in the general population?

PLOD2 p.Ala660Val (c.1979C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLOD2 p.Ala660Val (c.1979C>T)?

AlphaMissense predicts likely benign (score 0.3028) — an in-silico prediction, not a clinical call.

PLOD2 p.Ala660Val

c.1979C>T · VCV3934569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3028 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3028	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -6.85	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 90 kb · p 0.85 · regional, not allelic
Overall
CADD	26.4	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A639V vs ClinVar A660V) — 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.Ala660Val
Coding: c.1979C>T
MANE Select: NM_182943
Type: single nucleotide variant
Location: chr3:146071293 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.63
Residue 639 UniProt numbering: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLOD2 p.Arg205Met Uncertain significance ★★ ⚠ same condition
PLOD2 p.Arg495Gln Uncertain significance ★★ ⚠ same condition
PLOD2 p.Asn255Ile Uncertain significance ★★ ⚠ same condition
PLOD2 p.Asp293Asn Uncertain significance ★★ ⚠ same condition
PLOD2 p.Asp316Gly Uncertain significance ★★ ⚠ same condition
PLOD2 p.Asp348Tyr Uncertain significance ★★ ⚠ same condition
PLOD2 p.Glu112Gly Uncertain significance ★★ ⚠ same condition
PLOD2 p.Gly77Asp 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-ala660val (accessed [today's date]).

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