Is APCDD1L p.Leu31Pro (c.92T>C) pathogenic?

APCDD1L p.Leu31Pro (c.92T>C) is classified Uncertain significance in APCDD1L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely benign (0.0835); Rare (popmax 0.106%, afr).

How common is APCDD1L p.Leu31Pro (c.92T>C) in the general population?

APCDD1L p.Leu31Pro (c.92T>C) is rare (popmax 0.106%, afr) (gnomAD).

What do computational predictors say about APCDD1L p.Leu31Pro (c.92T>C)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

APCDD1L p.Leu31Pro

c.92T>C · rs763906482 · VCV2262884

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.106%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -5.02	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 2.6	GERP 2, phastCons 0.91
Regional constraint	o/e 0.99	unconstrained · MANE · 54 kb · p 0.77 · regional, not allelic
Overall
CADD	19.91	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.106% African / African-American · 78/73,380 alleles

Filtering AF 0.0873% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0803%

Overall 0.00562% 87/1,548,200 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.106%	941
Admixed American	0.0137%	7,297
Remaining individualsnot grpmax-eligible	0.00333%	30,021

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: APCDD1L
Protein: p.Leu31Pro
Coding: c.92T>C
MANE Select: NM_153360
dbSNP: rs763906482
Type: single nucleotide variant
Location: chr20:58470705 (GRCh38)
Gene constraint: LOEUF 1.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.31

Full APCDD1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APCDD1L p.Ala141Val Uncertain significance ★ ⚠ same type
APCDD1L p.Ala159Glu Uncertain significance ★ ⚠ same type
APCDD1L p.Ala246Ser Uncertain significance ★ ⚠ same type
APCDD1L p.Ala333Thr Uncertain significance ★ ⚠ same type
APCDD1L p.Ala3Ser Uncertain significance ★ ⚠ same type
APCDD1L p.Arg139His Uncertain significance ★ ⚠ same type
APCDD1L p.Arg139Pro Uncertain significance ★ ⚠ same type
APCDD1L p.Arg153Cys 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/apcdd1l-p-leu31pro (accessed [today's date]).

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