Is ACD p.Leu76Pro (c.227T>C) pathogenic?

ACD p.Leu76Pro (c.227T>C) is classified Uncertain significance in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-24). AlphaMissense: likely pathogenic (0.676); No allele count reported in gnomAD v4.1 (AN 1,602,286); Associated with Inborn genetic diseases.

What condition is associated with ACD p.Leu76Pro (c.227T>C)?

ACD p.Leu76Pro (c.227T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ACD p.Leu76Pro (c.227T>C) in the general population?

ACD p.Leu76Pro (c.227T>C) is no allele count reported in gnomAD v4.1 (AN 1,602,286) (gnomAD).

What do computational predictors say about ACD p.Leu76Pro (c.227T>C)?

AlphaMissense predicts likely pathogenic (score 0.676) — an in-silico prediction, not a clinical call.

ACD p.Leu76Pro

c.227T>C · rs2543610041 · VCV1743637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.676 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,602,286)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.676	likely pathogenic · top 10% in ACD
REVEL	0.225	benign-leaning
SaProt	LLR -14.63	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,611 bp · p 0.011 · regional, not allelic
Overall
CADD	28.1	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

No allele count reported in gnomAD v4.1 (AN 1,602,286). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACD
Protein: p.Leu76Pro
Coding: c.227T>C
MANE Select: NM_001082486
dbSNP: rs2543610041
Type: single nucleotide variant
Location: chr16:67659918 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 76: an α-helix

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.Leu76Gln Uncertain significance ★ ⚠ same residue
ACD p.Leu76= 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-leu76pro (accessed [today's date]).

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