Is APCDD1L p.Ser103Pro (c.307T>C) pathogenic?

APCDD1L p.Ser103Pro (c.307T>C) is classified Uncertain significance in APCDD1L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely pathogenic (0.9511); Absent from gnomAD v4.1.

How common is APCDD1L p.Ser103Pro (c.307T>C) in the general population?

APCDD1L p.Ser103Pro (c.307T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APCDD1L p.Ser103Pro (c.307T>C)?

AlphaMissense predicts likely pathogenic (score 0.9511) — an in-silico prediction, not a clinical call.

APCDD1L p.Ser103Pro

c.307T>C · rs2516101820 · VCV3127785

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9511 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9511	likely pathogenic · top 4% in APCDD1L
REVEL	0.402	indeterminate
SaProt	LLR -15.04	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP -3.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 54 kb · p 0.77 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: APCDD1L
Protein: p.Ser103Pro
Coding: c.307T>C
MANE Select: NM_153360
dbSNP: rs2516101820
Type: single nucleotide variant
Location: chr20:58467540 (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.Ser103Leu Uncertain significance ★ ⚠ same residue
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

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-ser103pro (accessed [today's date]).

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