Is ALPG p.His172= (c.516T>C) pathogenic?

ALPG p.His172= (c.516T>C) is classified Benign/Likely benign in ALPG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-01). Rare (popmax 0.903%, afr).

How common is ALPG p.His172= (c.516T>C) in the general population?

ALPG p.His172= (c.516T>C) is rare (popmax 0.903%, afr) (gnomAD).

ALPG p.His172=

c.516T>C · rs113898433 · VCV781828

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.903%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	0.228	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.903% African / African-American · 678/75,042 alleles

Filtering AF 0.847% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.825%

Overall 0.409% 6,595/1,613,438 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.38%	73
African / African-Americangrpmax	0.903%	111
Middle Eastern	0.627%	159
Remaining individualsnot grpmax-eligible	0.469%	213
European (non-Finnish)	0.404%	248
South Asian	0.265%	378
Amishnot grpmax-eligible	0.219%	456
Admixed American	0.155%	645
Finnishnot grpmax-eligible	0.117%	857
East Asian	0.00891%	11,218

Ashkenazi Jewish 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: ALPG
Protein: p.His172=
Coding: c.516T>C
MANE Select: NM_031313
dbSNP: rs113898433
Type: single nucleotide variant
Location: chr2:232407885 (GRCh38)
Gene constraint: LOEUF 1.103 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.31
Residue 172: a disulfide bond

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

Similar variants

ALPG p.Arg498Pro Benign ★★ same type
ALPG p.Gly230= Benign ★★ same type
ALPG p.Gly500Asp Likely benign ★★ same type
ALPG p.Leu8= Benign ★★ same type
ALPG p.Pro228Arg Benign ★★ ⚠ same type
ALPG p.Pro94Ser Benign ★★ ⚠ same type
ALPG p.Ser150= Benign ★★ same type
ALPG p.Tyr95Phe 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-his172 (accessed [today's date]).

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