Is PCNT p.Ala607Val (c.1820C>T) pathogenic?

PCNT p.Ala607Val (c.1820C>T) is classified Uncertain significance in PCNT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-15). AlphaMissense: likely benign (0.0827); Ultra-rare (popmax 0.0356%, eas); Associated with Inborn genetic diseases.

What condition is associated with PCNT p.Ala607Val (c.1820C>T)?

PCNT p.Ala607Val (c.1820C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PCNT p.Ala607Val (c.1820C>T) in the general population?

PCNT p.Ala607Val (c.1820C>T) is ultra-rare (popmax 0.0356%, eas) (gnomAD).

What do computational predictors say about PCNT p.Ala607Val (c.1820C>T)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

PCNT p.Ala607Val

c.1820C>T · rs146189038 · VCV1437953

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.044	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 -3	GERP -2
Regional constraint	o/e 1.03	unconstrained · MANE · 121 kb · p 0.027 · regional, not allelic
Overall
CADD	0.982	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 0.0356% East Asian · 16/44,892 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.0136% 220/1,613,932 alleles · ultra-rare exomes 213/1,461,700 · genomes 7/152,232 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0356%	2,806
Remaining individualsnot grpmax-eligible	0.024%	4,166
European (non-Finnish)	0.0153%	6,556
Admixed American	0.00666%	15,004
African / African-American	0.00534%	18,735
South Asian	0.0011%	91,090

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.Ala607Val
Coding: c.1820C>T
MANE Select: NM_006031
dbSNP: rs146189038
Type: single nucleotide variant
Location: chr21:46355510 (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.Ala607= Likely benign ★ same residue
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

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-ala607val (accessed [today's date]).

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