Is APCDD1 p.Val150Ile (c.448G>A) pathogenic?

APCDD1 p.Val150Ile (c.448G>A) is classified Benign in APCDD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0646); Common (popmax 16.8%, mid) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about APCDD1 p.Val150Ile (c.448G>A)?

AlphaMissense predicts likely benign (score 0.0646) — an in-silico prediction, not a clinical call.

APCDD1 p.Val150Ile

Q: How common is APCDD1 p.Val150Ile (c.448G>A) in the general population?

APCDD1 p.Val150Ile (c.448G>A) is common (popmax 16.8%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.448G>A · rs3748415 · VCV1286582

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0646 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 16.8%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0646	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -6.91	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 6.6	GERP 1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 33 kb · p 0.062 · regional, not allelic
Overall
CADD	18.31	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 16.8% Middle Eastern · 1,019/6,062 alleles

Filtering AF 16.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.2%

Overall 12% 193,902/1,613,984 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	16.8%	6
South Asian	16.5%	6
Amishnot grpmax-eligible	12.9%	8
East Asian	12.7%	8
European (non-Finnish)	12.6%	8
Remaining individualsnot grpmax-eligible	11.6%	9
Finnishnot grpmax-eligible	10.3%	10
Ashkenazi Jewishnot grpmax-eligible	8.9%	11
Admixed American	8.22%	12
African / African-American	2.25%	45

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.Val150Ile
Coding: c.448G>A
MANE Select: NM_153000
dbSNP: rs3748415
Type: single nucleotide variant
Location: chr18:10471735 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 82.10
Residue 150: a UniProt-annotated variant site (in)

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-val150ile (accessed [today's date]).

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