Is CYTIP p.Glu318Asp (c.954G>C) pathogenic?

CYTIP p.Glu318Asp (c.954G>C) is classified Uncertain significance in CYTIP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). AlphaMissense: likely benign (0.0933); Very rare (popmax 0.00667%, amr).

How common is CYTIP p.Glu318Asp (c.954G>C) in the general population?

CYTIP p.Glu318Asp (c.954G>C) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about CYTIP p.Glu318Asp (c.954G>C)?

AlphaMissense predicts likely benign (score 0.0933) — an in-silico prediction, not a clinical call.

CYTIP p.Glu318Asp

c.954G>C · rs1289846616 · VCV2293860

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0933 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0933	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -5.99	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 -0.76	GERP -4.5
Regional constraint	o/e 0.96	unconstrained · MANE · 28 kb · p 0.42 · regional, not allelic
Overall
CADD	1.473	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 0.00667% Admixed American · 4/60,010 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000248% 4/1,614,110 alleles · very 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: CYTIP
Protein: p.Glu318Asp
Coding: c.954G>C
MANE Select: NM_004288
dbSNP: rs1289846616
Type: single nucleotide variant
Location: chr2:157415803 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.24 · 1 PDB

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

Similar variants

CYTIP p.Ala23Val Uncertain significance ★ ⚠ same type
CYTIP p.Ala273Pro Uncertain significance ★ ⚠ same type
CYTIP p.Ala60Thr Uncertain significance ★ ⚠ same type
CYTIP p.Arg237Trp Uncertain significance ★ ⚠ same type
CYTIP p.Arg239Gln Uncertain significance ★ ⚠ same type
CYTIP p.Arg276Gln Uncertain significance ★ ⚠ same type
CYTIP p.Arg276Trp Uncertain significance ★ ⚠ same type
CYTIP p.Arg330Gln 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/cytip-p-glu318asp (accessed [today's date]).

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