Is PCNT p.Phe1340Ile (c.4018T>A) pathogenic?

PCNT p.Phe1340Ile (c.4018T>A) is classified Uncertain significance in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.2356); Very rare (popmax 0.00669%, afr); Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Phe1340Ile (c.4018T>A)?

PCNT p.Phe1340Ile (c.4018T>A) is associated with Inborn genetic diseases (ClinVar).

How common is PCNT p.Phe1340Ile (c.4018T>A) in the general population?

PCNT p.Phe1340Ile (c.4018T>A) is very rare (popmax 0.00669%, afr) (gnomAD).

What do computational predictors say about PCNT p.Phe1340Ile (c.4018T>A)?

AlphaMissense predicts likely benign (score 0.2356) — an in-silico prediction, not a clinical call.

PCNT p.Phe1340Ile

c.4018T>A · VCV4627147

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2356 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2356	likely benign
REVEL	0.168	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 0.55	GERP -4.7, phastCons 0.27
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	16.19	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 0.00669% African / African-American · 5/74,780 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000375% 6/1,601,916 alleles · very rare exomes 4/1,449,854 · genomes 2/152,062 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00669%	14,956
European (non-Finnish)	8.51e-05%	1,174,536

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.Phe1340Ile
Coding: c.4018T>A
MANE Select: NM_006031
Type: single nucleotide variant
Location: chr21:46391178 (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.Phe1340= 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
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-phe1340ile (accessed [today's date]).

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