Is CORO6 p.Cys331Ser (c.991T>A) pathogenic?

CORO6 p.Cys331Ser (c.991T>A) is classified Uncertain significance in CORO6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). Very rare (popmax 0.000424%, nfe).

How common is CORO6 p.Cys331Ser (c.991T>A) in the general population?

CORO6 p.Cys331Ser (c.991T>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

CORO6 p.Cys331Ser

c.991T>A · VCV3496093

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.613	indeterminate
Splicing
SpliceAI	Δ0.28	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 5,686 bp · p 0.91 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,018 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00143% 23/1,612,650 alleles · very rare exomes 23/1,460,448 · genomes 0/152,202 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,973
Remaining individualsnot grpmax-eligible	0.0048%	20,814
European (non-Finnish)grpmax	0.000424%	235,803

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CORO6
Protein: p.Cys331Ser
Coding: c.991T>A
MANE Select: NM_032854
Type: single nucleotide variant
Location: chr17:29616715 (GRCh38)
Gene constraint: LOEUF 1.177 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.55 · 1 PDB

Full CORO6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CORO6 p.Ala143Thr Uncertain significance ★ same type
CORO6 p.Ala211Val Uncertain significance ★ same type
CORO6 p.Ala225Thr Uncertain significance ★ same type
CORO6 p.Ala372Ser Uncertain significance ★ same type
CORO6 p.Ala375Gly Uncertain significance ★ same type
CORO6 p.Ala452Thr Uncertain significance ★ same type
CORO6 p.Arg118His Uncertain significance ★ same type
CORO6 p.Arg133Cys 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/coro6-p-cys331ser (accessed [today's date]).

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