Is PCNT p.Cys117Ser (c.350G>C) pathogenic?

PCNT p.Cys117Ser (c.350G>C) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-02-17). AlphaMissense: likely benign (0.1051); Rare (popmax 0.346%, sas); Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Cys117Ser (c.350G>C)?

PCNT p.Cys117Ser (c.350G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PCNT p.Cys117Ser (c.350G>C) in the general population?

PCNT p.Cys117Ser (c.350G>C) is rare (popmax 0.346%, sas) (gnomAD).

What do computational predictors say about PCNT p.Cys117Ser (c.350G>C)?

AlphaMissense predicts likely benign (score 0.1051) — an in-silico prediction, not a clinical call.

PCNT p.Cys117Ser

c.350G>C · rs544254673 · VCV2168802

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1051 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.346%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1051	likely benign
REVEL	0.023	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 -0.61	GERP -0.6, phastCons 0.001
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	0.091	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 0.346% South Asian · 315/91,056 alleles

Filtering AF 0.314% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.302%

Overall 0.0204% 330/1,614,128 alleles · rare exomes 308/1,461,774 · genomes 22/152,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.346%	289
Middle Eastern	0.066%	1,514
Remaining individualsnot grpmax-eligible	0.016%	6,250
European (non-Finnish)	8.47e-05%	1,180,002

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.Cys117Ser
Coding: c.350G>C
MANE Select: NM_006031
dbSNP: rs544254673
Type: single nucleotide variant
Location: chr21:46334479 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)

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.Cys117Arg Conflicting classifications of pathogenicity ★ ⚠ 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-cys117ser (accessed [today's date]).

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