Is PLOD3 p.Val328Phe (c.982G>T) pathogenic?

PLOD3 p.Val328Phe (c.982G>T) is classified Uncertain significance in PLOD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-23). AlphaMissense: likely benign (0.2207); Very rare (popmax 8.48e-05%, nfe).

How common is PLOD3 p.Val328Phe (c.982G>T) in the general population?

PLOD3 p.Val328Phe (c.982G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about PLOD3 p.Val328Phe (c.982G>T)?

AlphaMissense predicts likely benign (score 0.2207) — an in-silico prediction, not a clinical call.

PLOD3 p.Val328Phe

c.982G>T · rs146795873 · VCV2091901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2207 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2207	likely benign
REVEL	0.359	indeterminate
SaProt	LLR -10.73	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.59	donor gain · deltas
Pangolin	Δ0.26	gain · loss 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.3	GERP -4.4
Regional constraint	o/e 1.06	unconstrained · MANE · 6,691 bp · p 0.12 · regional, not allelic
Overall
CADD	19.29	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 8.48e-05% European (non-Finnish) · 1/1,179,870 alleles

Overall 6.2e-05% 1/1,613,754 alleles · very rare exomes 1/1,461,766 · genomes 0/151,988 · 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: PLOD3
Protein: p.Val328Phe
Coding: c.982G>T
MANE Select: NM_001084
dbSNP: rs146795873
Type: single nucleotide variant
Location: chr7:101212553 (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 328: the 'accessory region' region; a β-strand

Full PLOD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLOD3 p.Val328Ala Uncertain significance ★ same residue
PLOD3 p.Val328Leu Uncertain significance ★ ⚠ same residue
PLOD3 c.1359-1G>C Likely pathogenic ★★ same type
PLOD3 p.Arg452Ter Pathogenic ★★ same type
PLOD3 p.Tyr630Ter Pathogenic/Likely pathogenic ★★ same type
PLOD3 c.338+6G>C Uncertain significance ★★ same type
PLOD3 p.Ala371Val Uncertain significance ★★ ⚠ same type
PLOD3 p.Ala431Thr 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/plod3-p-val328phe (accessed [today's date]).

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