Is AUNIP p.Ser67Cys (c.200C>G) pathogenic?

AUNIP p.Ser67Cys (c.200C>G) is classified Uncertain significance in AUNIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.2405); Very rare (popmax 0.0017%, nfe).

How common is AUNIP p.Ser67Cys (c.200C>G) in the general population?

AUNIP p.Ser67Cys (c.200C>G) is very rare (popmax 0.0017%, nfe) (gnomAD).

What do computational predictors say about AUNIP p.Ser67Cys (c.200C>G)?

AlphaMissense predicts likely benign (score 0.2405) — an in-silico prediction, not a clinical call.

AUNIP p.Ser67Cys

c.200C>G · VCV4185537

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2405 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2405	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -11.26	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.69 · regional, not allelic
Overall
CADD	28.2	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 0.0017% European (non-Finnish) · 20/1,179,856 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00137% 20/1,461,450 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: AUNIP
Protein: p.Ser67Cys
Coding: c.200C>G
MANE Select: NM_024037
Type: single nucleotide variant
Location: chr1:25837433 (GRCh38)
Gene constraint: LOEUF 1.691 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.65

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

Similar variants

AUNIP p.Ala10Ser Uncertain significance ★ ⚠ same type
AUNIP p.Ala326Val Uncertain significance ★ ⚠ same type
AUNIP p.Ala55Val Uncertain significance ★ ⚠ same type
AUNIP p.Arg144Lys Uncertain significance ★ ⚠ same type
AUNIP p.Arg233Ile Uncertain significance ★ ⚠ same type
AUNIP p.Arg266His Uncertain significance ★ ⚠ same type
AUNIP p.Arg296Trp Uncertain significance ★ ⚠ same type
AUNIP p.Asn240Lys 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/aunip-p-ser67cys (accessed [today's date]).

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