Is ALAD p.Arg84Lys (c.251G>A) pathogenic?

ALAD p.Arg84Lys (c.251G>A) is classified Uncertain significance in ALAD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-11). AlphaMissense: likely benign (0.1064); Rare (popmax 0.101%, afr).

How common is ALAD p.Arg84Lys (c.251G>A) in the general population?

ALAD p.Arg84Lys (c.251G>A) is rare (popmax 0.101%, afr) (gnomAD).

What do computational predictors say about ALAD p.Arg84Lys (c.251G>A)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

ALAD p.Arg84Lys

c.251G>A · rs149572240 · VCV2201581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -0.29	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 -0.11	GERP 1.9, phastCons 0.021
Regional constraint	o/e 0.72	unconstrained · MANE · 5,256 bp · p 6.2e-09 · regional, not allelic
Overall
CADD	14.25	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 0.101% African / African-American · 76/75,052 alleles

Filtering AF 0.0829% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0762%

Overall 0.00539% 87/1,614,086 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.101%	988
Admixed American	0.0133%	7,504
Remaining individualsnot grpmax-eligible	0.0048%	20,835

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: ALAD
Protein: p.Arg84Lys
Coding: c.251G>A
MANE Select: NM_000031
dbSNP: rs149572240
Type: single nucleotide variant
Location: chr9:113391537 (GRCh38)
Gene constraint: LOEUF 0.63 · pLI 0.10 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.34 · 4 PDB
Residue 84: a β-strand

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

Similar variants

ALAD p.Gly133Arg Likely pathogenic ★★ same type
ALAD c.*127C>T Uncertain significance ★★ same type
ALAD c.*363G>A Uncertain significance ★★ same type
ALAD p.Ala93Thr Uncertain significance ★★ ⚠ same type
ALAD p.Arg147Cys Uncertain significance ★★ ⚠ same type
ALAD p.Arg174His Uncertain significance ★★ ⚠ same type
ALAD p.Arg17Gln Uncertain significance ★★ ⚠ same type
ALAD p.Arg222Cys 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/alad-p-arg84lys (accessed [today's date]).

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