Is APC2 p.Phe2037= (c.6111C>T) pathogenic?

APC2 p.Phe2037= (c.6111C>T) is classified Uncertain significance in APC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-14). Ultra-rare (popmax 0.0138%, amr); Associated with intellectual developmental disorder, autosomal recessive 74.

What condition is associated with APC2 p.Phe2037= (c.6111C>T)?

APC2 p.Phe2037= (c.6111C>T) is associated with intellectual developmental disorder, autosomal recessive 74 (ClinVar).

How common is APC2 p.Phe2037= (c.6111C>T) in the general population?

APC2 p.Phe2037= (c.6111C>T) is ultra-rare (popmax 0.0138%, amr) (gnomAD).

APC2 p.Phe2037=

c.6111C>T · rs1405418055 · VCV1033036

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0138%, amr)

Conditions

intellectual developmental disorder, autosomal recessive 74

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 0.16	GERP -1.7, phastCons 0.98
Overall
CADD	6.622	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0138% Admixed American · 3/21,772 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.000287% 3/1,047,082 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: APC2
Protein: p.Phe2037=
Coding: c.6111C>T
MANE Select: NM_005883
dbSNP: rs1405418055
Type: single nucleotide variant
Location: chr19:1469412 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.87
Residue 2037: a UniProt-annotated variant site (in cdcbm10)

Full APC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder, autosomal recessive 74 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APC2 p.Ala1703Glu Uncertain significance ★★ ⚠ same condition
APC2 p.Ala791Val Uncertain significance ★★ ⚠ same condition
APC2 p.Arg1539Pro Uncertain significance ★★ ⚠ same condition
APC2 p.Arg1708Leu Uncertain significance ★★ ⚠ same condition
APC2 p.Gly1007Ser Uncertain significance ★★ ⚠ same condition
APC2 p.Gly1958Arg Uncertain significance ★★ ⚠ same condition
APC2 p.Pro1327Ser Uncertain significance ★★ ⚠ same condition
APC2 p.Pro1864Leu 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/apc2-p-phe2037 (accessed [today's date]).

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