Is PCNT p.Arg403Trp (c.1207C>T) pathogenic?

PCNT p.Arg403Trp (c.1207C>T) is classified Uncertain significance in PCNT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-21). AlphaMissense: likely benign (0.0692); Ultra-rare (popmax 0.0267%, afr); Associated with PCNT-related disorder.

What condition is associated with PCNT p.Arg403Trp (c.1207C>T)?

PCNT p.Arg403Trp (c.1207C>T) is associated with PCNT-related disorder (ClinVar).

How common is PCNT p.Arg403Trp (c.1207C>T) in the general population?

PCNT p.Arg403Trp (c.1207C>T) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about PCNT p.Arg403Trp (c.1207C>T)?

AlphaMissense predicts likely benign (score 0.0692) — an in-silico prediction, not a clinical call.

PCNT p.Arg403Trp

c.1207C>T · rs538614143 · VCV2634761

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0692 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

PCNT-related disorder

Computational evidence

Protein change
AlphaMissense	0.0692	likely benign
REVEL	0.048	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 0.097	GERP -0.2, phastCons 0.94
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	15.95	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 0.0267% African / African-American · 20/74,986 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0018% 29/1,612,372 alleles · ultra-rare exomes 22/1,460,120 · genomes 7/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,749
European (non-Finnish)	0.000764%	130,944

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.Arg403Trp
Coding: c.1207C>T
MANE Select: NM_006031
dbSNP: rs538614143
Type: single nucleotide variant
Location: chr21:46349186 (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

PCNT-related disorder

Similar variants

PCNT p.Arg403= Likely benign ★ same residue
PCNT c.3313-2A>C Likely pathogenic ★★ same condition
PCNT c.7024+1G>A Likely pathogenic ★★ same condition
PCNT c.7691-1G>A Likely pathogenic ★★ same condition
PCNT c.8065-1G>C Likely pathogenic ★★ same condition
PCNT p.Arg3236Ter Pathogenic/Likely pathogenic ★★ same condition
PCNT p.Gln1689Ter Likely pathogenic ★★ same condition
PCNT p.Gln490Ter Pathogenic ★★ 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-arg403trp (accessed [today's date]).

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