Is ALDOC p.Phe282Leu (c.844T>C) pathogenic?

ALDOC p.Phe282Leu (c.844T>C) is classified Likely benign in ALDOC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-07). AlphaMissense: likely benign (0.1404); Very rare (popmax 0.00585%, nfe).

How common is ALDOC p.Phe282Leu (c.844T>C) in the general population?

ALDOC p.Phe282Leu (c.844T>C) is very rare (popmax 0.00585%, nfe) (gnomAD).

What do computational predictors say about ALDOC p.Phe282Leu (c.844T>C)?

AlphaMissense predicts likely benign (score 0.1404) — an in-silico prediction, not a clinical call.

ALDOC p.Phe282Leu

c.844T>C · VCV3520256

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1404 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00585%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1404	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -0.65	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 8.3	GERP 0.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 2,003 bp · p 1.9e-08 · regional, not allelic
Overall
CADD	18.01	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 0.00585% European (non-Finnish) · 69/1,180,036 alleles

Filtering AF 0.0047% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00431%

Overall 0.00489% 79/1,614,216 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00625%	16,008
European (non-Finnish)grpmax	0.00585%	17,102
Admixed American	0.005%	20,007
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Remaining individualsnot grpmax-eligible	0.0016%	62,510
African / African-American	0.00133%	75,072

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ALDOC
Protein: p.Phe282Leu
Coding: c.844T>C
MANE Select: NM_005165
Type: single nucleotide variant
Location: chr17:28573890 (GRCh38)
Gene constraint: LOEUF 0.785 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.43 · 1 PDB
Residue 282: an α-helix

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

Similar variants

ALDOC p.Ala136Asp Uncertain significance ★ ⚠ same type
ALDOC p.Ala297Thr Uncertain significance ★ ⚠ same type
ALDOC p.Ala297Val Uncertain significance ★ ⚠ same type
ALDOC p.Ala32Ser Uncertain significance ★ ⚠ same type
ALDOC p.Arg134Cys Uncertain significance ★ ⚠ same type
ALDOC p.Arg134His Uncertain significance ★ ⚠ same type
ALDOC p.Arg149Cys Uncertain significance ★ ⚠ same type
ALDOC p.Arg157Cys 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/aldoc-p-phe282leu (accessed [today's date]).

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