Is PCNT p.Pro79Leu (c.236C>T) pathogenic?

PCNT p.Pro79Leu (c.236C>T) is classified Conflicting classifications of pathogenicity in PCNT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-30). AlphaMissense: likely benign (0.0878); Ultra-rare (popmax 0.0637%, sas); Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Pro79Leu (c.236C>T)?

PCNT p.Pro79Leu (c.236C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCNT p.Pro79Leu (c.236C>T) in the general population?

PCNT p.Pro79Leu (c.236C>T) is ultra-rare (popmax 0.0637%, sas) (gnomAD).

What do computational predictors say about PCNT p.Pro79Leu (c.236C>T)?

AlphaMissense predicts likely benign (score 0.0878) — an in-silico prediction, not a clinical call.

PCNT p.Pro79Leu

c.236C>T · rs745598788 · VCV1337387

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0878 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0637%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0878	likely benign
REVEL	0.038	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 1.1	GERP -0.58, phastCons 0.013
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	14.28	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 0.0637% South Asian · 58/91,084 alleles

Filtering AF 0.0505% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0458%

Overall 0.0039% 63/1,614,132 alleles · ultra-rare exomes 60/1,461,772 · genomes 3/152,360 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0637%	1,570
Remaining individualsnot grpmax-eligible	0.0064%	15,623
African / African-American	0.00133%	75,062

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.Pro79Leu
Coding: c.236C>T
MANE Select: NM_006031
dbSNP: rs745598788
Type: single nucleotide variant
Location: chr21:46326558 (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

Similar variants

PCNT p.Gln910Ter Pathogenic ★★ same condition
PCNT p.Ala1194Val Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1400Thr Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1457Val Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1827Ser Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1827Thr Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1831Val Uncertain significance ★★ ⚠ same condition
PCNT p.Ala1964Val Uncertain significance ★★ ⚠ 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-pro79leu (accessed [today's date]).

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