Is CBLC p.Ser115Phe (c.344C>T) pathogenic?

CBLC p.Ser115Phe (c.344C>T) is classified Uncertain significance in CBLC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: ambiguous (0.3681); Very rare (popmax 0.00589%, afr).

How common is CBLC p.Ser115Phe (c.344C>T) in the general population?

CBLC p.Ser115Phe (c.344C>T) is very rare (popmax 0.00589%, afr) (gnomAD).

What do computational predictors say about CBLC p.Ser115Phe (c.344C>T)?

AlphaMissense predicts ambiguous (score 0.3681) — an in-silico prediction, not a clinical call.

CBLC p.Ser115Phe

c.344C>T · VCV3827890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00589%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3681	ambiguous
REVEL	0.647	pathogenic-leaning
SaProt	LLR -15.21	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.049, phastCons 0.004
Regional constraint	o/e 1.18	unconstrained · MANE · 3,282 bp · p 0.0054 · regional, not allelic
Overall
CADD	23.5	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 0.00589% African / African-American · 4/67,942 alleles

Filtering AF 0.00295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00262%

Overall 0.00327% 47/1,436,816 alleles · very rare exomes 40/1,284,712 · genomes 7/152,104 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00589%	16,986
European (non-Finnish)	0.00392%	25,526

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: CBLC
Protein: p.Ser115Phe
Coding: c.344C>T
MANE Select: NM_012116
Type: single nucleotide variant
Location: chr19:44778275 (GRCh38)
Gene constraint: LOEUF 1.058 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.85 · 7 PDB
Residue 115: the cbl-ptb domain; the '4h' region

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

Similar variants

CBLC p.Ala122Ser Uncertain significance ★ ⚠ same type
CBLC p.Ala137Val Uncertain significance ★ ⚠ same type
CBLC p.Ala21Val Uncertain significance ★ ⚠ same type
CBLC p.Ala377Pro Uncertain significance ★ same type
CBLC p.Ala398Val Uncertain significance ★ ⚠ same type
CBLC p.Ala433Ser Uncertain significance ★ ⚠ same type
CBLC p.Ala450Gly Uncertain significance ★ ⚠ same type
CBLC p.Ala465Val 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/cblc-p-ser115phe (accessed [today's date]).

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