Is PLOD1 p.Pro24Ser (c.70C>T) pathogenic?

PLOD1 p.Pro24Ser (c.70C>T) is classified Uncertain significance in PLOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-30). AlphaMissense: likely benign (0.0942); Ultra-rare (popmax 0.0518%, mid); Associated with Ehlers-Danlos syndrome.

What condition is associated with PLOD1 p.Pro24Ser (c.70C>T)?

PLOD1 p.Pro24Ser (c.70C>T) is associated with Ehlers-Danlos syndrome (ClinVar).

How common is PLOD1 p.Pro24Ser (c.70C>T) in the general population?

PLOD1 p.Pro24Ser (c.70C>T) is ultra-rare (popmax 0.0518%, mid) (gnomAD).

What do computational predictors say about PLOD1 p.Pro24Ser (c.70C>T)?

AlphaMissense predicts likely benign (score 0.0942) — an in-silico prediction, not a clinical call.

PLOD1 p.Pro24Ser

c.70C>T · rs1395571164 · VCV1702261

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0942 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0518%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ehlers-Danlos syndrome

Computational evidence

Protein change
AlphaMissense	0.0942	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -5.32	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 1.4	GERP -1.4, phastCons 0.99
Regional constraint	o/e 0.93	unconstrained · MANE · 40 kb · p 0.03 · regional, not allelic
Overall
CADD	20.8	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0518% Middle Eastern · 3/5,786 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00752%

Overall 0.00039% 6/1,538,376 alleles · ultra-rare exomes 6/1,386,102 · genomes 0/152,274 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0518%	1,929
Admixed American	0.00197%	50,778
European (non-Finnish)	0.000175%	572,626

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: PLOD1
Protein: p.Pro24Ser
Coding: c.70C>T
MANE Select: NM_000302
dbSNP: rs1395571164
Type: single nucleotide variant
Location: chr1:11934849 (GRCh38)
Gene constraint: LOEUF 0.938 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.04

Full PLOD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ehlers-Danlos syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLOD1 p.Pro24Arg Uncertain significance ★★ ⚠ same residue
PLOD1 p.Pro24= Likely benign ★★ same residue
PLOD1 p.Pro24Leu Uncertain significance ★ ⚠ same residue
PLOD1 p.Pro24Thr Uncertain significance ★ ⚠ same residue
PLOD1 p.Arg319Ter Pathogenic ★★ same condition
PLOD1 p.Gln636Ter Pathogenic/Likely pathogenic ★★ same condition
PLOD1 p.Tyr511Ter Pathogenic ★★ same condition
PLOD1 p.Arg259Cys 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/plod1-p-pro24ser (accessed [today's date]).

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