Is SUB1 p.Ala48= (c.144C>T) pathogenic?

SUB1 p.Ala48= (c.144C>T) is classified Likely benign in SUB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-26). Ultra-rare (popmax 0.0236%, amr).

How common is SUB1 p.Ala48= (c.144C>T) in the general population?

SUB1 p.Ala48= (c.144C>T) is ultra-rare (popmax 0.0236%, amr) (gnomAD).

SUB1 p.Ala48=

c.144C>T · rs771797879 · VCV754372

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0236%, amr)

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 -3.2	GERP -3.6
Overall
CADD	8.458	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0236% Admixed American · 14/59,346 alleles

Filtering AF 0.0142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.000994% 16/1,609,524 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0236%	4,239
Remaining individualsnot grpmax-eligible	0.00161%	62,298
African / African-American	0.00134%	74,434

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: SUB1
Protein: p.Ala48=
Coding: c.144C>T
MANE Select: NM_006713
dbSNP: rs771797879
Type: single nucleotide variant
Location: chr5:32591634 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 77.03 · 6 PDB
Residue 48: the 'disordered' region; the 'regulatory' region

Full SUB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SUB1 c.196-10T>A Benign ★★ same type
SUB1 p.Ala32Ser Uncertain significance ★ ⚠ same type
SUB1 p.Asp60Glu Uncertain significance ★ ⚠ same type
SUB1 p.Gln54Arg Uncertain significance ★ ⚠ same type
SUB1 p.Ser57Cys Uncertain significance ★ ⚠ same type
SUB1 p.Ser57Gly Uncertain significance ★ ⚠ same type
SUB1 p.Ser73Asn 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/sub1-p-ala48 (accessed [today's date]).

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