Is CCDC191 p.Asp187Glu (c.561T>A) pathogenic?

CCDC191 p.Asp187Glu (c.561T>A) is classified Uncertain significance in CCDC191 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely pathogenic (0.845); Rare (popmax 0.266%, mid).

How common is CCDC191 p.Asp187Glu (c.561T>A) in the general population?

CCDC191 p.Asp187Glu (c.561T>A) is rare (popmax 0.266%, mid) (gnomAD).

What do computational predictors say about CCDC191 p.Asp187Glu (c.561T>A)?

AlphaMissense predicts likely pathogenic (score 0.845) — an in-silico prediction, not a clinical call.

CCDC191 p.Asp187Glu

c.561T>A · rs150401939 · VCV2310726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.845 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.266%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.845	likely pathogenic · top 2% in CCDC191
REVEL	0.288	benign-leaning
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 91 kb · p 0.00055 · regional, not allelic
Overall
CADD	21.5	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 0.266% Middle Eastern · 16/6,024 alleles

Filtering AF 0.167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.0371% 595/1,602,830 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.266%	377
Admixed American	0.152%	657
Remaining individualsnot grpmax-eligible	0.0646%	1,547
European (non-Finnish)	0.0375%	2,668
African / African-American	0.00807%	12,398
Ashkenazi Jewishnot grpmax-eligible	0.00683%	14,651
South Asian	0.00111%	89,692

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: CCDC191
Protein: p.Asp187Glu
Coding: c.561T>A
MANE Select: NM_020817
dbSNP: rs150401939
Type: single nucleotide variant
Location: chr3:114036641 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36

Full CCDC191 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC191 p.Ala331Thr Uncertain significance ★ ⚠ same type
CCDC191 p.Ala347Thr Uncertain significance ★ ⚠ same type
CCDC191 p.Ala415Thr Uncertain significance ★ ⚠ same type
CCDC191 p.Ala596Ser Uncertain significance ★ ⚠ same type
CCDC191 p.Ala669Val Uncertain significance ★ ⚠ same type
CCDC191 p.Ala800Asp Uncertain significance ★ ⚠ same type
CCDC191 p.Ala800Val Uncertain significance ★ ⚠ same type
CCDC191 p.Arg19Leu 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/ccdc191-p-asp187glu (accessed [today's date]).

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