Is PCNT p.Arg288His (c.863G>A) pathogenic?

PCNT p.Arg288His (c.863G>A) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-12-27). AlphaMissense: likely benign (0.0707); Ultra-rare (popmax 0.024%, afr); Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Arg288His (c.863G>A)?

PCNT p.Arg288His (c.863G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PCNT p.Arg288His (c.863G>A) in the general population?

PCNT p.Arg288His (c.863G>A) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about PCNT p.Arg288His (c.863G>A)?

AlphaMissense predicts likely benign (score 0.0707) — an in-silico prediction, not a clinical call.

PCNT p.Arg288His

c.863G>A · rs542099749 · VCV1444252

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0707 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0707	likely benign
REVEL	0.025	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 3.6	GERP -3.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	17.61	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 0.024% African / African-American · 18/74,986 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00485% 78/1,607,070 alleles · ultra-rare exomes 66/1,454,698 · genomes 12/152,372 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,166
Remaining individualsnot grpmax-eligible	0.00643%	15,563
European (non-Finnish)	0.00467%	21,411
Admixed American	0.0017%	58,926

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.Arg288His
Coding: c.863G>A
MANE Select: NM_006031
dbSNP: rs542099749
Type: single nucleotide variant
Location: chr21:46346885 (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.Arg288Cys Uncertain significance ★ ⚠ 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-arg288his (accessed [today's date]).

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