Is POPDC1 p.Ser201Phe (c.602C>T) pathogenic?

POPDC1 p.Ser201Phe (c.602C>T) is classified Likely pathogenic in POPDC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-08). AlphaMissense: likely pathogenic (0.9993); Very rare (popmax 0.000339%, nfe); Associated with autosomal recessive limb-girdle muscular dystrophy type 2X.

What condition is associated with POPDC1 p.Ser201Phe (c.602C>T)?

POPDC1 p.Ser201Phe (c.602C>T) is associated with autosomal recessive limb-girdle muscular dystrophy type 2X (ClinVar).

How common is POPDC1 p.Ser201Phe (c.602C>T) in the general population?

POPDC1 p.Ser201Phe (c.602C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is BVES-related limb-girdle muscular dystrophy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about POPDC1 p.Ser201Phe (c.602C>T)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

POPDC1 p.Ser201Phe

c.602C>T · rs869025337 · VCV222033

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2X

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 1% in POPDC1
REVEL	0.755	pathogenic-leaning
SaProt	LLR -16.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 32 kb · p 0.55 · regional, not allelic
Overall
CADD	31.0	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 0.000339% European (non-Finnish) · 4/1,179,086 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,460,688 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: POPDC1
Protein: p.Ser201Phe
Coding: c.602C>T
MANE Select: NM_001199563
dbSNP: rs869025337
Type: single nucleotide variant
Location: chr6:105124593 (GRCh38)
Structure: AlphaFold pLDDT 76.08
Residue 201: a UniProt-annotated variant site (in lgmdr25; reduces membrane localization of popdc1 and popdc2; decreases by 50% affinity for camp; disrupts enhancement of kckn2 surface expression; increases kckn2 outward currents; no effect on total protein levels)

Full POPDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2X — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For BVES-related limb-girdle muscular dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult

Similar variants

BVES p.Ser201Cys Likely pathogenic ★ same residue
POPDC1 p.Arg88Ter Pathogenic/Likely pathogenic ★★ same condition
POPDC1 p.Arg129Gln Uncertain significance ★★ ⚠ same condition
POPDC1 p.Arg172His Uncertain significance ★★ ⚠ same condition
POPDC1 p.Arg311Gln Uncertain significance ★★ ⚠ same condition
POPDC1 p.Arg88Gln Uncertain significance ★★ ⚠ same condition
POPDC1 p.Asp304Asn Uncertain significance ★★ ⚠ same condition
POPDC1 p.His279Arg 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/popdc1-p-ser201phe (accessed [today's date]).

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