Is PCNT p.Val856Met (c.2566G>A) pathogenic?

PCNT p.Val856Met (c.2566G>A) is classified Benign/Likely benign in PCNT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-08). AlphaMissense: likely benign (0.1111); Rare (popmax 0.315%, amr).

How common is PCNT p.Val856Met (c.2566G>A) in the general population?

PCNT p.Val856Met (c.2566G>A) is rare (popmax 0.315%, amr) (gnomAD).

What do computational predictors say about PCNT p.Val856Met (c.2566G>A)?

AlphaMissense predicts likely benign (score 0.1111) — an in-silico prediction, not a clinical call.

PCNT p.Val856Met

c.2566G>A · rs143023746 · VCV708156

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1111 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.315%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1111	likely benign
REVEL	0.042	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 0.045	GERP 1.1
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	8.923	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 0.315% Admixed American · 189/60,014 alleles

Filtering AF 0.278% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.264%

Overall 0.0134% 216/1,611,828 alleles · rare exomes 186/1,459,468 · genomes 30/152,360 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.315%	318
African / African-American	0.0227%	4,415
Remaining individualsnot grpmax-eligible	0.0016%	62,442
South Asian	0.0011%	91,064
European (non-Finnish)	0.000678%	147,451

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.Val856Met
Coding: c.2566G>A
MANE Select: NM_006031
dbSNP: rs143023746
Type: single nucleotide variant
Location: chr21:46363891 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)

Full PCNT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PCNT p.Val856Gly Uncertain significance ★ ⚠ same residue
PCNT c.1032+1G>A Pathogenic/Likely pathogenic ★★ same type
PCNT c.1680-1G>C Likely pathogenic ★★ same type
PCNT c.3313-2A>C Likely pathogenic ★★ same type
PCNT c.5995-2A>C Likely pathogenic ★★ same type
PCNT c.7024+1G>A Likely pathogenic ★★ same type
PCNT c.7024+1G>C Likely pathogenic ★★ same type
PCNT c.7691-1G>A Likely pathogenic ★★ same type

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-val856met (accessed [today's date]).

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