Is PCNT p.Ile1877= (c.5631C>T) pathogenic?

PCNT p.Ile1877= (c.5631C>T) is classified Benign in PCNT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 44.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with microcephalic osteodysplastic primordial dwarfism type II.

What condition is associated with PCNT p.Ile1877= (c.5631C>T)?

PCNT p.Ile1877= (c.5631C>T) is associated with microcephalic osteodysplastic primordial dwarfism type II (ClinVar).

PCNT p.Ile1877=

Q: How common is PCNT p.Ile1877= (c.5631C>T) in the general population?

PCNT p.Ile1877= (c.5631C>T) is common (popmax 44.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5631C>T · rs16979162 · VCV95337

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 44.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

microcephalic osteodysplastic primordial dwarfism type II

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.5	GERP -5.1
Overall
CADD	0.237	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 44.5% African / African-American · 33,362/75,000 alleles

Filtering AF 44.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 43.9%

Overall 9.03% 145,591/1,612,646 alleles · common exomes 118,621/1,460,394 · genomes 26,970/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	44.5%	2
Finnishnot grpmax-eligible	10.4%	10
Remaining individualsnot grpmax-eligible	9.9%	10
South Asian	8.52%	12
Ashkenazi Jewishnot grpmax-eligible	8.5%	12
Middle Eastern	7.44%	13
European (non-Finnish)	7.17%	14
Admixed American	6.78%	15
Amishnot grpmax-eligible	2.74%	36
East Asian	0.214%	467

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.Ile1877=
Coding: c.5631C>T
MANE Select: NM_006031
dbSNP: rs16979162
Type: single nucleotide variant
Location: chr21:46411704 (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-ile1877 (accessed [today's date]).

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