Is ASB15 p.Ala72Ser (c.214G>T) pathogenic?

ASB15 p.Ala72Ser (c.214G>T) is classified Uncertain significance in ASB15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-09). AlphaMissense: likely benign (0.1772); Very rare (popmax 0.000596%, nfe).

How common is ASB15 p.Ala72Ser (c.214G>T) in the general population?

ASB15 p.Ala72Ser (c.214G>T) is very rare (popmax 0.000596%, nfe) (gnomAD).

What do computational predictors say about ASB15 p.Ala72Ser (c.214G>T)?

AlphaMissense predicts likely benign (score 0.1772) — an in-silico prediction, not a clinical call.

ASB15 p.Ala72Ser

c.214G>T · VCV3434480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1772 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000596%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1772	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -6.71	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 7.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 22 kb · p 0.3 · regional, not allelic
Overall
CADD	18.15	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000596% European (non-Finnish) · 7/1,173,964 alleles

Filtering AF 0.000248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000436% 7/1,607,002 alleles · very rare

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: ASB15
Protein: p.Ala72Ser
Coding: c.214G>T
MANE Select: NM_001290258
Type: single nucleotide variant
Location: chr7:123616417 (GRCh38)
Gene constraint: LOEUF 1.186 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.39

Full ASB15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB15 p.Ala72Val Uncertain significance ★ ⚠ same residue
ASB15 p.Ala194Thr Uncertain significance ★ ⚠ same type
ASB15 p.Ala250Thr Uncertain significance ★ ⚠ same type
ASB15 p.Ala315Gly Uncertain significance ★ ⚠ same type
ASB15 p.Ala372Thr Uncertain significance ★ ⚠ same type
ASB15 p.Ala558Val Uncertain significance ★ ⚠ same type
ASB15 p.Ala568Pro Uncertain significance ★ ⚠ same type
ASB15 p.Arg189Gln 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/asb15-p-ala72ser (accessed [today's date]).

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