Is CCDC191 p.Ser121Ile (c.362G>T) pathogenic?

CCDC191 p.Ser121Ile (c.362G>T) is classified Uncertain significance in CCDC191 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.1065); Ultra-rare (popmax 0.0137%, eas).

How common is CCDC191 p.Ser121Ile (c.362G>T) in the general population?

CCDC191 p.Ser121Ile (c.362G>T) is ultra-rare (popmax 0.0137%, eas) (gnomAD).

What do computational predictors say about CCDC191 p.Ser121Ile (c.362G>T)?

AlphaMissense predicts likely benign (score 0.1065) — an in-silico prediction, not a clinical call.

CCDC191 p.Ser121Ile

c.362G>T · rs779081372 · VCV3139038

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1065 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1065	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -7.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.25	GERP -3.3
Regional constraint	o/e 0.90	unconstrained · MANE · 91 kb · p 0.00055 · regional, not allelic
Overall
CADD	13.04	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0137% East Asian · 6/43,864 alleles

Filtering AF 0.0059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00401%

Overall 0.000414% 6/1,448,150 alleles · ultra-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: CCDC191
Protein: p.Ser121Ile
Coding: c.362G>T
MANE Select: NM_020817
dbSNP: rs779081372
Type: single nucleotide variant
Location: chr3:114042756 (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-ser121ile (accessed [today's date]).

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