Is PLIN1 p.Ala208= (c.624C>T) pathogenic?

PLIN1 p.Ala208= (c.624C>T) is classified Likely benign in PLIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-12). Very rare (popmax 8.47e-05%, nfe).

How common is PLIN1 p.Ala208= (c.624C>T) in the general population?

PLIN1 p.Ala208= (c.624C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

PLIN1 p.Ala208=

c.624C>T · VCV4926588

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP -4.8, phastCons 0.006
Overall
CADD	6.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,002 alleles

Overall 6.2e-05% 1/1,614,052 alleles · very rare exomes 1/1,461,792 · genomes 0/152,260 · 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: PLIN1
Protein: p.Ala208=
Coding: c.624C>T
MANE Select: NM_002666
Type: single nucleotide variant
Location: chr15:89669647 (GRCh38)
Gene constraint: LOEUF 1.201 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.52
Residue 208: the 'disordered' region

Full PLIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLIN1 p.Ala361Glu Uncertain significance ★★ ⚠ same type
PLIN1 p.Arg125Cys Uncertain significance ★★ ⚠ same type
PLIN1 p.Glu151Lys Uncertain significance ★★ ⚠ same type
PLIN1 p.Leu404Phe Uncertain significance ★★ ⚠ same type
PLIN1 p.Leu90Pro Uncertain significance ★★ ⚠ same type
PLIN1 p.Thr345Ala Uncertain significance ★★ ⚠ same type
PLIN1 c.1209+9C>T Benign ★★ same type
PLIN1 c.251-153G>T Benign ★★ 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/plin1-p-ala208 (accessed [today's date]).

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