Is ASB14 p.Cys320Phe (c.959G>T) pathogenic?

ASB14 p.Cys320Phe (c.959G>T) is classified Uncertain significance in ASB14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: ambiguous (0.3911); Very rare (popmax 0.00769%, sas).

How common is ASB14 p.Cys320Phe (c.959G>T) in the general population?

ASB14 p.Cys320Phe (c.959G>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about ASB14 p.Cys320Phe (c.959G>T)?

AlphaMissense predicts ambiguous (score 0.3911) — an in-silico prediction, not a clinical call.

ASB14 p.Cys320Phe

c.959G>T · VCV3788395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3911 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3911	ambiguous
REVEL	0.222	benign-leaning
SaProt	LLR -7.56	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 15 kb · p 0.61 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00769% South Asian · 7/91,020 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000547% 8/1,461,508 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,003
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: ASB14
Protein: p.Cys320Phe
Coding: c.959G>T
MANE Select: NM_001142733
Type: single nucleotide variant
Location: chr3:57278849 (GRCh38)
Gene constraint: LOEUF 1.35 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.24

Full ASB14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB14 p.Ala104Val Uncertain significance ★ ⚠ same type
ASB14 p.Ala221Thr Uncertain significance ★ ⚠ same type
ASB14 p.Ala257Thr Uncertain significance ★ ⚠ same type
ASB14 p.Ala297Gly Uncertain significance ★ ⚠ same type
ASB14 p.Ala33Ser Uncertain significance ★ ⚠ same type
ASB14 p.Ala363Pro Uncertain significance ★ ⚠ same type
ASB14 p.Ala378Val Uncertain significance ★ ⚠ same type
ASB14 p.Ala48Thr 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/asb14-p-cys320phe (accessed [today's date]).

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