Is PCNT p.Ser682Trp (c.2045C>G) pathogenic?

PCNT p.Ser682Trp (c.2045C>G) is classified Uncertain significance in PCNT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-06). AlphaMissense: likely benign (0.2155); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Ser682Trp (c.2045C>G)?

PCNT p.Ser682Trp (c.2045C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PCNT p.Ser682Trp (c.2045C>G) in the general population?

PCNT p.Ser682Trp (c.2045C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PCNT p.Ser682Trp (c.2045C>G)?

AlphaMissense predicts likely benign (score 0.2155) — an in-silico prediction, not a clinical call.

PCNT p.Ser682Trp

c.2045C>G · VCV4627137

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2155 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2155	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.01	GERP 0.26
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	17.73	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,002 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00112% 18/1,613,740 alleles · very rare exomes 16/1,461,564 · genomes 2/152,176 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.00136%	73,734

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: PCNT
Protein: p.Ser682Trp
Coding: c.2045C>G
MANE Select: NM_006031
Type: single nucleotide variant
Location: chr21:46357082 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 682: a modified residue (phosphoserine)

Full PCNT 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

PCNT p.Ser682= Likely benign ★ same residue
PCNT p.Gln910Ter Pathogenic ★★ same condition
PCNT p.Ala1194Val Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1400Thr Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1457Val Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1827Ser Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1827Thr Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1831Val 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/pcnt-p-ser682trp (accessed [today's date]).

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