Is PLEC p.Val1050Phe (c.3148G>T) pathogenic?

PLEC p.Val1050Phe (c.3148G>T) is classified Uncertain significance in PLEC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). AlphaMissense: likely benign (0.2283); No allele count reported in gnomAD v4.1 (AN 1,602,694); Associated with epidermolysis bullosa simplex with nail dystrophy.

What condition is associated with PLEC p.Val1050Phe (c.3148G>T)?

PLEC p.Val1050Phe (c.3148G>T) is associated with epidermolysis bullosa simplex with nail dystrophy, epidermolysis bullosa simplex 5A, Ogna type, epidermolysis bullosa simplex 5B, with muscular dystrophy (ClinVar).

How common is PLEC p.Val1050Phe (c.3148G>T) in the general population?

PLEC p.Val1050Phe (c.3148G>T) is no allele count reported in gnomAD v4.1 (AN 1,602,694) (gnomAD).

What do computational predictors say about PLEC p.Val1050Phe (c.3148G>T)?

AlphaMissense predicts likely benign (score 0.2283) — an in-silico prediction, not a clinical call.

PLEC p.Val1050Phe

c.3148G>T · VCV3751288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2283 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,602,694)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

epidermolysis bullosa simplex with nail dystrophy

Computational evidence

Protein change
AlphaMissense	0.2283	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 18 kb · p 4.9e-10 · regional, not allelic
Overall
CADD	17.66	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 is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V1187F vs ClinVar V1050F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,602,694). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PLEC
Protein: p.Val1050Phe
Coding: c.3148G>T
MANE Select: NM_201384
Type: single nucleotide variant
Location: chr8:143929215 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)

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

Disease context

epidermolysis bullosa simplex with nail dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epidermolysis bullosa simplex 5A, Ogna type epidermolysis bullosa simplex 5B, with muscular dystrophy epidermolysis bullosa simplex 5C, with pyloric atresia autosomal recessive limb-girdle muscular dystrophy type 2Q

Similar variants

PLEC p.Val1050Leu Uncertain significance ★ ⚠ same residue
PLEC p.Arg1490Ter Pathogenic/Likely pathogenic ★★ same condition
PLEC p.Arg1973Trp Pathogenic ★★ ⚠ same condition
PLEC p.Arg2027Ter Pathogenic ★★ same condition
PLEC p.Arg2292Ter Pathogenic ★★ same condition
PLEC p.Arg2324Ter Pathogenic ★★ same condition
PLEC p.Arg2394Ter Pathogenic ★★ same condition
PLEC p.Arg559Ter Pathogenic ★★ 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/plec-p-val1050phe (accessed [today's date]).

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