Is CITED4 p.Asp172Glu (c.516C>G) pathogenic?

CITED4 p.Asp172Glu (c.516C>G) is classified Uncertain significance in CITED4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely pathogenic (0.5883); Very rare (popmax 0.000268%, nfe).

How common is CITED4 p.Asp172Glu (c.516C>G) in the general population?

CITED4 p.Asp172Glu (c.516C>G) is very rare (popmax 0.000268%, nfe) (gnomAD).

What do computational predictors say about CITED4 p.Asp172Glu (c.516C>G)?

AlphaMissense predicts likely pathogenic (score 0.5883) — an in-silico prediction, not a clinical call.

CITED4 p.Asp172Glu

c.516C>G · VCV4653948

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5883 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000268%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5883	likely pathogenic
REVEL	0.69	pathogenic-leaning
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -0.33, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 551 bp · p 0.00038 · regional, not allelic
Overall
CADD	25.8	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 0.000268% European (non-Finnish) · 3/1,118,322 alleles

Filtering AF 7.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000226% 3/1,326,574 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: CITED4
Protein: p.Asp172Glu
Coding: c.516C>G
MANE Select: NM_133467
Type: single nucleotide variant
Location: chr1:40861612 (GRCh38)
Gene constraint: LOEUF 1.958 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.74

Full CITED4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CITED4 p.Ala116Thr Uncertain significance ★ ⚠ same type
CITED4 p.Ala22Gly Uncertain significance ★ ⚠ same type
CITED4 p.Ala28Val Uncertain significance ★ ⚠ same type
CITED4 p.Ala93Glu Uncertain significance ★ ⚠ same type
CITED4 p.Arg155Cys Uncertain significance ★ ⚠ same type
CITED4 p.Arg155Gly Uncertain significance ★ ⚠ same type
CITED4 p.Arg30Gln Uncertain significance ★ ⚠ same type
CITED4 p.Arg30Trp 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/cited4-p-asp172glu (accessed [today's date]).

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