Is APC p.Asp183Val (c.548A>T) pathogenic?

APC p.Asp183Val (c.548A>T) is classified Uncertain significance in APC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-26). AlphaMissense: likely pathogenic (0.9891); Very rare (popmax 0.00167%, amr); Associated with familial adenomatous polyposis 1.

What condition is associated with APC p.Asp183Val (c.548A>T)?

APC p.Asp183Val (c.548A>T) is associated with familial adenomatous polyposis 1, hereditary neoplastic syndrome (ClinVar).

How common is APC p.Asp183Val (c.548A>T) in the general population?

APC p.Asp183Val (c.548A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Familial adenomatous polyposis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about APC p.Asp183Val (c.548A>T)?

AlphaMissense predicts likely pathogenic (score 0.9891) — an in-silico prediction, not a clinical call.

APC p.Asp183Val

c.548A>T · rs1758239334 · VCV940817

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

familial adenomatous polyposis 1

Computational evidence

Protein change
AlphaMissense	0.9891	likely pathogenic · top 7% in APC
REVEL	0.816	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 61 kb · p 0.82 · regional, not allelic
Overall
CADD	27.2	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,974 alleles

Overall 6.2e-05% 1/1,611,700 alleles · very rare exomes 0/1,459,496 · genomes 1/152,204 · joint denominator

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: APC
Protein: p.Asp183Val
Coding: c.548A>T
MANE Select: NM_000038
dbSNP: rs1758239334
Type: single nucleotide variant
Location: chr5:112780806 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 183: an α-helix

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

Disease context

familial adenomatous polyposis 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Familial adenomatous polyposis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

APC p.Asp183Gly Uncertain significance ★★ ⚠ same residue
APC p.Asp183His Uncertain significance ★★ ⚠ same residue
APC p.Asp183= Likely benign ★★ same residue
APC p.Asp183fs Pathogenic ★ same residue
APC p.Asp183Ala Uncertain significance ★ ⚠ same residue
APC c.1312+3A>C Likely pathogenic ★★★ same condition
APC c.1312+3A>G Pathogenic ★★★ same condition
APC c.1312+5G>A Likely pathogenic ★★★ 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/apc-p-asp183val (accessed [today's date]).

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