Is PCNT p.Ala595Val (c.1784C>T) pathogenic?

PCNT p.Ala595Val (c.1784C>T) is classified Likely benign in PCNT (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.0787); Rare (popmax 0.849%, afr); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Ala595Val (c.1784C>T)?

PCNT p.Ala595Val (c.1784C>T) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Ala595Val (c.1784C>T) in the general population?

PCNT p.Ala595Val (c.1784C>T) is rare (popmax 0.849%, afr) (gnomAD).

What do computational predictors say about PCNT p.Ala595Val (c.1784C>T)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

PCNT p.Ala595Val

c.1784C>T · rs143028464 · VCV340473

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.849%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

microcephalic osteodysplastic primordial dwarfism type II

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.032	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 -0.43	GERP -2.5
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	1.298	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 0.849% African / African-American · 637/75,058 alleles

Filtering AF 0.794% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.772%

Overall 0.0507% 819/1,613,992 alleles · rare exomes 456/1,461,644 · genomes 363/152,348 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.849%	118
Admixed American	0.0866%	1,154
Remaining individualsnot grpmax-eligible	0.072%	1,389
East Asian	0.0579%	1,726
European (non-Finnish)	0.00475%	21,072
South Asian	0.00329%	30,363

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.Ala595Val
Coding: c.1784C>T
MANE Select: NM_006031
dbSNP: rs143028464
Type: single nucleotide variant
Location: chr21:46355474 (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 p.Ala595= Likely benign ★ same residue
PCNT p.Ala595Thr Likely benign ★ 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

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-ala595val (accessed [today's date]).

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