Is C2CD4B p.Leu162Pro (c.485T>C) pathogenic?

C2CD4B p.Leu162Pro (c.485T>C) is classified Likely benign in C2CD4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: likely benign (0.0398); Absent from gnomAD v4.1.

How common is C2CD4B p.Leu162Pro (c.485T>C) in the general population?

C2CD4B p.Leu162Pro (c.485T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about C2CD4B p.Leu162Pro (c.485T>C)?

AlphaMissense predicts likely benign (score 0.0398) — an in-silico prediction, not a clinical call.

C2CD4B p.Leu162Pro

c.485T>C · VCV3993989

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0398 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,207,230)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0398	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -4.96	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 -0.059	GERP -2.5
Regional constraint	o/e 1.11	unconstrained · MANE · 1,091 bp · p 0.0058 · regional, not allelic
Overall
CADD	1.853	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

No allele count reported in gnomAD v4.1 (AN 1,207,230). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: C2CD4B
Protein: p.Leu162Pro
Coding: c.485T>C
MANE Select: NM_001007595
Type: single nucleotide variant
Location: chr15:62164500 (GRCh38)
Structure: AlphaFold pLDDT 60.81
Residue 162: the 'disordered' region

Full C2CD4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C2CD4B p.Ala138Thr Uncertain significance ★ ⚠ same type
C2CD4B p.Ala190Gly Uncertain significance ★ ⚠ same type
C2CD4B p.Ala197Val Uncertain significance ★ ⚠ same type
C2CD4B p.Ala20Asp Uncertain significance ★ ⚠ same type
C2CD4B p.Ala231Pro Uncertain significance ★ ⚠ same type
C2CD4B p.Ala239Val Uncertain significance ★ ⚠ same type
C2CD4B p.Ala244Thr Uncertain significance ★ ⚠ same type
C2CD4B p.Ala244Val 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/c2cd4b-p-leu162pro (accessed [today's date]).

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