Is PCNT p.Arg312Trp (c.934C>T) pathogenic?

PCNT p.Arg312Trp (c.934C>T) is classified Uncertain significance in PCNT (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-11-10). AlphaMissense: likely benign (0.1529); Ultra-rare (popmax 0.0202%, mid); Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Arg312Trp (c.934C>T)?

PCNT p.Arg312Trp (c.934C>T) is associated with Inborn genetic diseases, microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Arg312Trp (c.934C>T) in the general population?

PCNT p.Arg312Trp (c.934C>T) is ultra-rare (popmax 0.0202%, mid) (gnomAD).

What do computational predictors say about PCNT p.Arg312Trp (c.934C>T)?

AlphaMissense predicts likely benign (score 0.1529) — an in-silico prediction, not a clinical call.

PCNT p.Arg312Trp

c.934C>T · rs572076735 · VCV429553

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1529 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0202%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1529	likely benign
REVEL	0.045	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 0.052	GERP 0.9
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	25.8	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 0.0202% Middle Eastern · 1/4,948 alleles

Filtering AF 0.00957% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00733%

Overall 0.00739% 118/1,596,716 alleles · ultra-rare exomes 95/1,444,456 · genomes 23/152,260 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0202%	4,948
Admixed American	0.0178%	5,615
Remaining individualsnot grpmax-eligible	0.0145%	6,881
Finnishnot grpmax-eligible	0.0143%	6,972
African / African-American	0.00801%	12,491
South Asian	0.00682%	14,660
European (non-Finnish)	0.00639%	15,650
East Asian	0.00452%	22,136

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.Arg312Trp
Coding: c.934C>T
MANE Select: NM_006031
dbSNP: rs572076735
Type: single nucleotide variant
Location: chr21:46346956 (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

Also linked: microcephalic osteodysplastic primordial dwarfism type II

Similar variants

PCNT p.Arg312Gln Uncertain significance ⚠ same residue
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

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-arg312trp (accessed [today's date]).

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