Is PLOD3 p.Arg313= (c.939C>T) pathogenic?

PLOD3 p.Arg313= (c.939C>T) is classified Benign in PLOD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Common (popmax 7.87%, eas) — too common for a highly-penetrant pathogenic allele.

PLOD3 p.Arg313=

Q: How common is PLOD3 p.Arg313= (c.939C>T) in the general population?

PLOD3 p.Arg313= (c.939C>T) is common (popmax 7.87%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.939C>T · rs1546840 · VCV1180052

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 7.87%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.023	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.33	GERP 1.8, phastCons 0.015
Overall
CADD	11.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.87% East Asian · 3,532/44,858 alleles

Filtering AF 7.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.57%

Overall 0.851% 13,741/1,613,868 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	7.87%	13
African / African-American	2.83%	35
Remaining individualsnot grpmax-eligible	1.27%	79
South Asian	1.18%	85
Admixed American	0.63%	159
Middle Eastern	0.562%	178
European (non-Finnish)	0.489%	205
Ashkenazi Jewishnot grpmax-eligible	0.0879%	1,138
Finnishnot grpmax-eligible	0.0187%	5,336

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.Arg313=
Coding: c.939C>T
MANE Select: NM_001084
dbSNP: rs1546840
Type: single nucleotide variant
Location: chr7:101212596 (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 313: the 'accessory region' region; an α-helix

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

Similar variants

PLOD3 p.Arg313His 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
PLOD3 p.Ala59Val 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-arg313 (accessed [today's date]).

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