Is ACD p.Pro127Ser (c.379C>T) pathogenic?

ACD p.Pro127Ser (c.379C>T) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-30). AlphaMissense: likely pathogenic (0.6506); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ACD p.Pro127Ser (c.379C>T)?

ACD p.Pro127Ser (c.379C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACD p.Pro127Ser (c.379C>T) in the general population?

ACD p.Pro127Ser (c.379C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ACD p.Pro127Ser (c.379C>T)?

AlphaMissense predicts likely pathogenic (score 0.6506) — an in-silico prediction, not a clinical call.

ACD p.Pro127Ser

c.379C>T · VCV3480250

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6506 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6506	likely pathogenic
REVEL	0.256	benign-leaning
SaProt	LLR -7.73	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	25.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACD
Protein: p.Pro127Ser
Coding: c.379C>T
MANE Select: NM_001082486
Type: single nucleotide variant
Location: chr16:67659571 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 127: a β-strand

Full ACD 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

ACD p.Pro127Leu Uncertain significance ★ ⚠ same residue
ACD p.Pro127= Likely benign ★ same residue
ACD c.-20C>T Uncertain significance ★★ same condition
ACD c.-26T>G Uncertain significance ★★ same condition
ACD c.-29C>A Uncertain significance ★★ same condition
ACD c.-30C>T Uncertain significance ★★ same condition
ACD c.-35C>T Uncertain significance ★★ same condition
ACD c.-36C>G 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/acd-p-pro127ser (accessed [today's date]).

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