Is PLOD3 p.Val90Phe (c.268G>T) pathogenic?

PLOD3 p.Val90Phe (c.268G>T) is classified Uncertain significance in PLOD3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-08). AlphaMissense: likely pathogenic (0.9518); Very rare (popmax 0.00119%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PLOD3 p.Val90Phe (c.268G>T)?

PLOD3 p.Val90Phe (c.268G>T) is associated with Inborn genetic diseases (ClinVar).

How common is PLOD3 p.Val90Phe (c.268G>T) in the general population?

PLOD3 p.Val90Phe (c.268G>T) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about PLOD3 p.Val90Phe (c.268G>T)?

AlphaMissense predicts likely pathogenic (score 0.9518) — an in-silico prediction, not a clinical call.

PLOD3 p.Val90Phe

c.268G>T · rs1192783718 · VCV2107093

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9518 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9518	likely pathogenic
REVEL	0.38	indeterminate
SaProt	LLR -14.38	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 3.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 6,691 bp · p 0.12 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% European (non-Finnish) · 14/1,179,990 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000958% 14/1,461,824 alleles · very rare

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: PLOD3
Protein: p.Val90Phe
Coding: c.268G>T
MANE Select: NM_001084
dbSNP: rs1192783718
Type: single nucleotide variant
Location: chr7:101216480 (GRCh38)
Gene constraint: LOEUF 0.925 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.80 · 18 PDB
Residue 90: the 'required for glycosyltransferase activity' region; an α-helix

Full PLOD3 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

PLOD3 p.Val90Ile Uncertain significance ★ ⚠ same residue
PLOD3 c.338+6G>C Uncertain significance ★★ same condition
PLOD3 p.Ala59Val Uncertain significance ★★ ⚠ same condition
PLOD3 p.Ala646Val Uncertain significance ★★ ⚠ same condition
PLOD3 p.Arg135His Uncertain significance ★★ ⚠ same condition
PLOD3 p.Arg181His Uncertain significance ★★ ⚠ same condition
PLOD3 p.Arg313His Uncertain significance ★★ ⚠ same condition
PLOD3 p.Arg317Gln 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/plod3-p-val90phe (accessed [today's date]).

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