Is PCNT p.Arg320Lys (c.959G>A) pathogenic?

PCNT p.Arg320Lys (c.959G>A) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.1308); Ultra-rare (popmax 0.0198%, nfe); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Arg320Lys (c.959G>A)?

PCNT p.Arg320Lys (c.959G>A) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Arg320Lys (c.959G>A) in the general population?

PCNT p.Arg320Lys (c.959G>A) is ultra-rare (popmax 0.0198%, nfe) (gnomAD).

What do computational predictors say about PCNT p.Arg320Lys (c.959G>A)?

AlphaMissense predicts likely benign (score 0.1308) — an in-silico prediction, not a clinical call.

PCNT p.Arg320Lys

c.959G>A · rs149844283 · VCV197781

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1308 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

microcephalic osteodysplastic primordial dwarfism type II

Computational evidence

Protein change
AlphaMissense	0.1308	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	Δ0.94	donor loss · deltas
Constraint at this position
Conservation	phyloP 1.6	GERP -0.24, phastCons 0.002
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	20.6	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 0.0198% European (non-Finnish) · 232/1,173,690 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0168%

Overall 0.0147% 235/1,595,728 alleles · ultra-rare exomes 216/1,443,474 · genomes 19/152,254 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0198%	5,059
African / African-American	0.00401%	24,945

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.Arg320Lys
Coding: c.959G>A
MANE Select: NM_006031
dbSNP: rs149844283
Type: single nucleotide variant
Location: chr21:46346981 (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

microcephalic osteodysplastic primordial dwarfism type II — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PCNT c.1032+1G>A Pathogenic/Likely pathogenic ★★ same condition
PCNT c.1680-1G>C Likely pathogenic ★★ same condition
PCNT c.5995-2A>C Likely pathogenic ★★ same condition
PCNT c.7024+1G>C Likely pathogenic ★★ same condition
PCNT c.7691-1G>A Likely pathogenic ★★ same condition
PCNT c.9624-2A>G Likely pathogenic ★★ same condition
PCNT p.Arg1730Ter Pathogenic/Likely pathogenic ★★ same condition
PCNT p.Arg1923Ter Pathogenic/Likely 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-arg320lys (accessed [today's date]).

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