Is PCNT p.Thr191Pro (c.571A>C) pathogenic?

PCNT p.Thr191Pro (c.571A>C) is classified Uncertain significance in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-27). AlphaMissense: likely benign (0.0495); Ultra-rare (popmax 0.0165%, mid); Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Thr191Pro (c.571A>C)?

PCNT p.Thr191Pro (c.571A>C) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

How common is PCNT p.Thr191Pro (c.571A>C) in the general population?

PCNT p.Thr191Pro (c.571A>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about PCNT p.Thr191Pro (c.571A>C)?

AlphaMissense predicts likely benign (score 0.0495) — an in-silico prediction, not a clinical call.

PCNT p.Thr191Pro

c.571A>C · rs150001244 · VCV897155

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0495 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

microcephalic osteodysplastic primordial dwarfism type II

Computational evidence

Protein change
AlphaMissense	0.0495	likely benign
REVEL	0.053	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 -0.33	GERP -0.18
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	0.894	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 0.0165% Middle Eastern · 1/6,066 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000622% 10/1,607,036 alleles · ultra-rare exomes 7/1,459,284 · genomes 3/147,752 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,066
Ashkenazi Jewishnot grpmax-eligible	0.00346%	28,930
East Asian	0.00225%	44,438
Admixed American	0.00168%	59,406
Finnishnot grpmax-eligible	0.00157%	63,644
European (non-Finnish)	0.000424%	235,577

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.Thr191Pro
Coding: c.571A>C
MANE Select: NM_006031
dbSNP: rs150001244
Type: single nucleotide variant
Location: chr21:46334700 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 191: a modified residue (phosphothreonine)

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.Thr191= 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
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-thr191pro (accessed [today's date]).

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