Is ASB16 p.Phe340Ser (c.1019T>C) pathogenic?

ASB16 p.Phe340Ser (c.1019T>C) is classified Uncertain significance in ASB16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely pathogenic (0.7528); Very rare (popmax 0.00105%, nfe).

How common is ASB16 p.Phe340Ser (c.1019T>C) in the general population?

ASB16 p.Phe340Ser (c.1019T>C) is very rare (popmax 0.00105%, nfe) (gnomAD).

What do computational predictors say about ASB16 p.Phe340Ser (c.1019T>C)?

AlphaMissense predicts likely pathogenic (score 0.7528) — an in-silico prediction, not a clinical call.

ASB16 p.Phe340Ser

c.1019T>C · VCV3788537

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7528 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00105%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7528	likely pathogenic · top 6% in ASB16
REVEL	0.329	indeterminate
SaProt	LLR -12.14	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP -1, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 7,597 bp · p 0.012 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00105% European (non-Finnish) · 12/1,143,402 alleles

Filtering AF 0.00056% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000442%

Overall 0.000865% 12/1,386,930 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: ASB16
Protein: p.Phe340Ser
Coding: c.1019T>C
MANE Select: NM_080863
Type: single nucleotide variant
Location: chr17:44177187 (GRCh38)
Gene constraint: LOEUF 1.675 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.68

Full ASB16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB16 p.Ala200Pro Uncertain significance ★ ⚠ same type
ASB16 p.Ala200Thr Uncertain significance ★ ⚠ same type
ASB16 p.Ala219Val Uncertain significance ★ ⚠ same type
ASB16 p.Ala252Pro Uncertain significance ★ ⚠ same type
ASB16 p.Ala254Thr Uncertain significance ★ ⚠ same type
ASB16 p.Ala273Gly Uncertain significance ★ ⚠ same type
ASB16 p.Ala291Thr Uncertain significance ★ ⚠ same type
ASB16 p.Ala310Thr 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/asb16-p-phe340ser (accessed [today's date]).

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