Is PCNT p.Ala2903Pro (c.8707G>C) pathogenic?

PCNT p.Ala2903Pro (c.8707G>C) is classified Benign in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2013-02-08). AlphaMissense: likely benign (0.1025); Absent from gnomAD v4.1.

How common is PCNT p.Ala2903Pro (c.8707G>C) in the general population?

PCNT p.Ala2903Pro (c.8707G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PCNT p.Ala2903Pro (c.8707G>C)?

AlphaMissense predicts likely benign (score 0.1025) — an in-silico prediction, not a clinical call.

PCNT p.Ala2903Pro

c.8707G>C · rs35147998 · VCV159676

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1025 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1025	likely benign
REVEL	0.104	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 2.1	GERP -0.003, phastCons 0.035
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	13.82	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.Ala2903Pro
Coding: c.8707G>C
MANE Select: NM_006031
dbSNP: rs35147998
Type: single nucleotide variant
Location: chr21:46432171 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 2903: a UniProt-annotated variant site (in); the 'disordered' region

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

Similar variants

PCNT p.Ala2903Thr Benign/Likely benign ★★ same residue
PCNT p.Ala2903= Likely benign ★ 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-ala2903pro (accessed [today's date]).

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