Is ALG10 p.Ser243= (c.729C>T) pathogenic?

ALG10 p.Ser243= (c.729C>T) is classified Benign in ALG10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-05). Common (popmax 9.33%, afr) — too common for a highly-penetrant pathogenic allele.

ALG10 p.Ser243=

Q: How common is ALG10 p.Ser243= (c.729C>T) in the general population?

ALG10 p.Ser243= (c.729C>T) is common (popmax 9.33%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.729C>T · rs78273253 · VCV776699

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 9.33%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP 0.043
Overall
CADD	3.753	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.33% African / African-American · 6,995/74,974 alleles

Filtering AF 9.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.07%

Overall 0.621% 10,029/1,613,954 alleles · common exomes 5,796/1,461,790 · genomes 4,233/152,164 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.33%	11
Admixed American	1.31%	77
Middle Eastern	1.29%	78
Remaining individualsnot grpmax-eligible	0.992%	101
Ashkenazi Jewishnot grpmax-eligible	0.544%	184
European (non-Finnish)	0.115%	867
South Asian	0.0329%	3,036
East Asian	0.00223%	44,872

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: ALG10
Protein: p.Ser243=
Coding: c.729C>T
MANE Select: NM_032834
dbSNP: rs78273253
Type: single nucleotide variant
Location: chr12:34026222 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.51

Full ALG10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALG10 p.Thr134= Benign ★★ same type
ALG10 p.Val269Ile Benign ★★ same type
ALG10 c.369+1G>T Likely pathogenic ★ same type
ALG10 p.Met61Val Likely pathogenic ★ ⚠ same type
ALG10 p.Ala11Asp Uncertain significance ★ ⚠ same type
ALG10 p.Ala11Thr Uncertain significance ★ ⚠ same type
ALG10 p.Ala125Thr Uncertain significance ★ ⚠ same type
ALG10 p.Ala12Asp 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/alg10-p-ser243 (accessed [today's date]).

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