Is ACD p.Ser224= (c.672C>T) pathogenic?

ACD p.Ser224= (c.672C>T) is classified Likely benign in ACD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-10). Ultra-rare (popmax 0.0134%, eas); Associated with Inborn genetic diseases.

What condition is associated with ACD p.Ser224= (c.672C>T)?

ACD p.Ser224= (c.672C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ACD p.Ser224= (c.672C>T) in the general population?

ACD p.Ser224= (c.672C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

ACD p.Ser224=

c.672C>T · rs759305698 · VCV1766524

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.1	GERP -0.84, phastCons 0.4
Overall
CADD	4.695	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,872 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000411% 6/1,461,194 alleles · ultra-rare

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: ACD
Protein: p.Ser224=
Coding: c.672C>T
MANE Select: NM_001082486
dbSNP: rs759305698
Type: single nucleotide variant
Location: chr16:67658790 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 63.09 · 28 PDB
Residue 224: the 'interaction with pot1' region; 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.Ser224Arg Uncertain significance ★ ⚠ same residue
ACD p.Ser224Asn Uncertain significance ★ ⚠ same residue
ACD p.Ser224Thr Uncertain significance ★ ⚠ 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

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-ser224 (accessed [today's date]).

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