Is PLEC p.Gln2575Arg (c.7724A>G) pathogenic?

PLEC p.Gln2575Arg (c.7724A>G) is classified Conflicting classifications of pathogenicity in PLEC (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-02). AlphaMissense: likely benign (0.064); Very rare (popmax 0.00695%, eas); Associated with Inborn genetic diseases.

What condition is associated with PLEC p.Gln2575Arg (c.7724A>G)?

PLEC p.Gln2575Arg (c.7724A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PLEC p.Gln2575Arg (c.7724A>G) in the general population?

PLEC p.Gln2575Arg (c.7724A>G) is very rare (popmax 0.00695%, eas) (gnomAD).

What do computational predictors say about PLEC p.Gln2575Arg (c.7724A>G)?

AlphaMissense predicts likely benign (score 0.064) — an in-silico prediction, not a clinical call.

PLEC p.Gln2575Arg

c.7724A>G · VCV4079726

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.064 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00695%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.064	likely benign
REVEL	0.107	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 -3.1
Regional constraint	o/e 1.08	unconstrained · MANE · 18 kb · p 4.9e-10 · regional, not allelic
Overall
CADD	0.28	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q2712R vs ClinVar Q2575R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00695% East Asian · 3/43,164 alleles

Filtering AF 0.00184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000911%

Overall 0.000384% 6/1,564,016 alleles · very rare exomes 5/1,411,964 · genomes 1/152,052 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00695%	14,388
Remaining individualsnot grpmax-eligible	0.00493%	20,301

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: PLEC
Protein: p.Gln2575Arg
Coding: c.7724A>G
MANE Select: NM_201384
Type: single nucleotide variant
Location: chr8:143922097 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLEC p.Ala1041Thr Uncertain significance ★★ ⚠ same condition
PLEC p.Ala1221Ser Uncertain significance ★★ ⚠ same condition
PLEC p.Ala1368Val Uncertain significance ★★ ⚠ same condition
PLEC p.Ala1390Val Uncertain significance ★★ ⚠ same condition
PLEC p.Ala1411Thr Uncertain significance ★★ ⚠ same condition
PLEC p.Ala1492Val Uncertain significance ★★ ⚠ same condition
PLEC p.Ala1513Val Uncertain significance ★★ ⚠ same condition
PLEC p.Ala1574Thr 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/plec-p-gln2575arg (accessed [today's date]).

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