Is PCNT p.Phe1940Ser (c.5819T>C) pathogenic?

PCNT p.Phe1940Ser (c.5819T>C) is classified Uncertain significance in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-29). AlphaMissense: likely pathogenic (0.7852); Absent from gnomAD v4.1.

How common is PCNT p.Phe1940Ser (c.5819T>C) in the general population?

PCNT p.Phe1940Ser (c.5819T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PCNT p.Phe1940Ser (c.5819T>C)?

AlphaMissense predicts likely pathogenic (score 0.7852) — an in-silico prediction, not a clinical call.

PCNT p.Phe1940Ser

c.5819T>C · rs1460538855 · VCV1426039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7852 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.7852	likely pathogenic · top 4% in PCNT
REVEL	0.116	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PCNT
Protein: p.Phe1940Ser
Coding: c.5819T>C
MANE Select: NM_006031
dbSNP: rs1460538855
Type: single nucleotide variant
Location: chr21:46411892 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)

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

Similar variants

PCNT p.Phe1940= Likely benign ★★ same residue
PCNT p.Phe1940fs Pathogenic ★ same residue
PCNT c.1032+1G>A Pathogenic/Likely pathogenic ★★ same type
PCNT c.1680-1G>C Likely pathogenic ★★ same type
PCNT c.3313-2A>C Likely pathogenic ★★ same type
PCNT c.5995-2A>C Likely pathogenic ★★ same type
PCNT c.7024+1G>A Likely pathogenic ★★ same type
PCNT c.7024+1G>C Likely pathogenic ★★ same type

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-phe1940ser (accessed [today's date]).

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