Is PCNT p.Arg2201Cys (c.6601C>T) pathogenic?

PCNT p.Arg2201Cys (c.6601C>T) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-07-17). AlphaMissense: likely benign (0.0771); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Arg2201Cys (c.6601C>T)?

PCNT p.Arg2201Cys (c.6601C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCNT p.Arg2201Cys (c.6601C>T) in the general population?

PCNT p.Arg2201Cys (c.6601C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about PCNT p.Arg2201Cys (c.6601C>T)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

PCNT p.Arg2201Cys

c.6601C>T · rs746840086 · VCV1901882

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.4	GERP -2.2
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	6.631	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,084 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00242% 39/1,613,494 alleles · very rare exomes 35/1,461,292 · genomes 4/152,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,771
European (non-Finnish)	0.00271%	36,869
East Asian	0.00223%	44,892
Admixed American	0.00167%	60,008
African / African-American	0.00133%	74,926

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.Arg2201Cys
Coding: c.6601C>T
MANE Select: NM_006031
dbSNP: rs746840086
Type: single nucleotide variant
Location: chr21:46416519 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 2201: the 'disordered' region

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.Arg2201His Likely benign ★ same residue
PCNT p.Arg2201= 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

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-arg2201cys (accessed [today's date]).

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