Is APCDD1 p.Thr407= (c.1221C>T) pathogenic?

APCDD1 p.Thr407= (c.1221C>T) is classified Likely benign in APCDD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-23). Ultra-rare (popmax 0.098%, eas).

How common is APCDD1 p.Thr407= (c.1221C>T) in the general population?

APCDD1 p.Thr407= (c.1221C>T) is ultra-rare (popmax 0.098%, eas) (gnomAD).

APCDD1 p.Thr407=

c.1221C>T · rs1267305223 · VCV792916

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.098%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.009, phastCons 1
Overall
CADD	10.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.098% East Asian · 44/44,890 alleles

Filtering AF 0.075% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0669%

Overall 0.00279% 45/1,614,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.098%	1,020
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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: APCDD1
Protein: p.Thr407=
Coding: c.1221C>T
MANE Select: NM_153000
dbSNP: rs1267305223
Type: single nucleotide variant
Location: chr18:10487714 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 82.10

Full APCDD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APCDD1 p.Ala176Thr Uncertain significance ★★ ⚠ same type
APCDD1 p.Ala343Thr Uncertain significance ★★ ⚠ same type
APCDD1 p.Arg169His Uncertain significance ★★ ⚠ same type
APCDD1 p.Arg213Gln Uncertain significance ★★ ⚠ same type
APCDD1 p.Arg303Cys Uncertain significance ★★ ⚠ same type
APCDD1 p.Arg344Trp Uncertain significance ★★ ⚠ same type
APCDD1 p.Arg432Gln Uncertain significance ★★ ⚠ same type
APCDD1 p.Glu393Lys Uncertain significance ★★ ⚠ same type

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/apcdd1-p-thr407 (accessed [today's date]).

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