Is ALPG p.Arg136Cys (c.406C>T) pathogenic?

ALPG p.Arg136Cys (c.406C>T) is classified Uncertain significance in ALPG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.2079); Ultra-rare (popmax 0.01%, amr).

How common is ALPG p.Arg136Cys (c.406C>T) in the general population?

ALPG p.Arg136Cys (c.406C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about ALPG p.Arg136Cys (c.406C>T)?

AlphaMissense predicts likely benign (score 0.2079) — an in-silico prediction, not a clinical call.

ALPG p.Arg136Cys

c.406C>T · rs764875560 · VCV3113160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2079 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2079	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -10.88	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.092	GERP -1.1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,395 bp · p 0.6 · regional, not allelic
Overall
CADD	22.3	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 0.01% Admixed American · 6/59,994 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00223% 36/1,613,682 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,999
East Asian	0.00445%	22,447
South Asian	0.0044%	22,741
African / African-American	0.00267%	37,467
European (non-Finnish)	0.00178%	56,191
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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: ALPG
Protein: p.Arg136Cys
Coding: c.406C>T
MANE Select: NM_031313
dbSNP: rs764875560
Type: single nucleotide variant
Location: chr2:232407699 (GRCh38)
Gene constraint: LOEUF 1.103 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.31

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

Similar variants

ALPG p.Arg136Leu Uncertain significance ★ ⚠ same residue
ALPG p.Arg498Pro Benign ★★ same type
ALPG p.Gly230= Benign ★★ same type
ALPG p.Gly500Asp Likely benign ★★ same type
ALPG p.His172= Benign/Likely benign ★★ same type
ALPG p.Leu8= Benign ★★ same type
ALPG p.Pro228Arg Benign ★★ ⚠ same type
ALPG p.Pro94Ser Benign ★★ ⚠ 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/alpg-p-arg136cys (accessed [today's date]).

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