Is ALG1 p.Lys72Arg (c.215A>G) pathogenic?

ALG1 p.Lys72Arg (c.215A>G) is classified Likely benign in ALG1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.0692); Very rare (popmax 0.004%, afr); Associated with intellectual disability.

What condition is associated with ALG1 p.Lys72Arg (c.215A>G)?

ALG1 p.Lys72Arg (c.215A>G) is associated with intellectual disability (ClinVar).

How common is ALG1 p.Lys72Arg (c.215A>G) in the general population?

ALG1 p.Lys72Arg (c.215A>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about ALG1 p.Lys72Arg (c.215A>G)?

AlphaMissense predicts likely benign (score 0.0692) — an in-silico prediction, not a clinical call.

ALG1 p.Lys72Arg

c.215A>G · rs768379497 · VCV975487

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0692 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0692	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -6.77	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 1.6	GERP -0.69, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 13 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	15.15	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 0.004% African / African-American · 3/74,908 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00031% 5/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,969
Remaining individualsnot grpmax-eligible	0.0016%	62,488
South Asian	0.0011%	91,092

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: ALG1
Protein: p.Lys72Arg
Coding: c.215A>G
MANE Select: NM_019109
dbSNP: rs768379497
Type: single nucleotide variant
Location: chr16:5072957 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

Full ALG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ALG1 p.Lys72Ile Uncertain significance ★★ ⚠ same residue
ALG1 p.Arg28Gln Likely benign same condition
ALG1 c.1187+1G>A Pathogenic/Likely pathogenic ★★ same type
ALG1 c.1187+2T>C Pathogenic ★★ same type
ALG1 c.1188-2A>G Pathogenic/Likely pathogenic ★★ same type
ALG1 c.209-2A>G Likely pathogenic ★★ same type
ALG1 c.539+1G>A Pathogenic/Likely pathogenic ★★ same type
ALG1 c.630-2A>G Likely pathogenic ★★ 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/alg1-p-lys72arg (accessed [today's date]).

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