Is PACS1 p.Ala26Val (c.77C>T) pathogenic?

PACS1 p.Ala26Val (c.77C>T) is classified Conflicting classifications of pathogenicity in PACS1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.1027); Very rare (popmax 0.00492%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PACS1 p.Ala26Val (c.77C>T)?

PACS1 p.Ala26Val (c.77C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PACS1 p.Ala26Val (c.77C>T) in the general population?

PACS1 p.Ala26Val (c.77C>T) is very rare (popmax 0.00492%, nfe) (gnomAD).

What do computational predictors say about PACS1 p.Ala26Val (c.77C>T)?

AlphaMissense predicts likely benign (score 0.1027) — an in-silico prediction, not a clinical call.

PACS1 p.Ala26Val

c.77C>T · rs1343494175 · VCV2457220

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1027 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1027	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.97, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 230 bp · p 0.06 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00492% European (non-Finnish) · 55/1,117,072 alleles

Filtering AF 0.00387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00347%

Overall 0.00388% 57/1,469,080 alleles · very rare exomes 44/1,317,528 · genomes 13/151,552 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00492%	20,310
Remaining individualsnot grpmax-eligible	0.00353%	28,351

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: PACS1
Protein: p.Ala26Val
Coding: c.77C>T
MANE Select: NM_018026
dbSNP: rs1343494175
Type: single nucleotide variant
Location: chr11:66070563 (GRCh38)
Gene constraint: LOEUF 0.3 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 65.81 · 1 PDB
Residue 26: the 'disordered' region

Full PACS1 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

PACS1 p.Asp691Asn Uncertain significance ★★ ⚠ same condition
PACS1 p.Gln36Glu Uncertain significance ★★ ⚠ same condition
PACS1 p.Leu664Phe Uncertain significance ★★ same condition
PACS1 p.Ser558Leu Uncertain significance ★★ same condition
PACS1 p.Ser57Phe Uncertain significance ★★ ⚠ same condition
PACS1 p.Ser845Leu Uncertain significance ★★ ⚠ same condition
PACS1 c.1293+6C>T Benign/Likely benign ★★ same condition
PACS1 c.2776+5G>A Benign/Likely benign ★★ 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/pacs1-p-ala26val (accessed [today's date]).

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