Is CRIP1 p.Cys52Phe (c.155G>T) pathogenic?

CRIP1 p.Cys52Phe (c.155G>T) is classified Benign in CRIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-05-30). AlphaMissense: likely pathogenic (0.993); Low-frequency (popmax 1.11%, nfe).

How common is CRIP1 p.Cys52Phe (c.155G>T) in the general population?

CRIP1 p.Cys52Phe (c.155G>T) is low-frequency (popmax 1.11%, nfe) (gnomAD).

What do computational predictors say about CRIP1 p.Cys52Phe (c.155G>T)?

AlphaMissense predicts likely pathogenic (score 0.993) — an in-silico prediction, not a clinical call.

CRIP1 p.Cys52Phe

c.155G>T · rs7824 · VCV770784

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.993 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.11%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.993	likely pathogenic · top 9% in CRIP1
REVEL	0.863	moderately pathogenic-leaning
SaProt	LLR -12.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 1,248 bp · p 0.039 · regional, not allelic
Overall
CADD	28.6	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 1.11% European (non-Finnish) · 13,137/1,179,994 alleles

Filtering AF 1.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.09%

Overall 0.982% 15,845/1,613,476 alleles · low-frequency exomes 14,321/1,461,152 · genomes 1,524/152,324 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.09%	32
European (non-Finnish)grpmax	1.11%	90
Remaining individualsnot grpmax-eligible	0.685%	146
Admixed American	0.24%	417
Ashkenazi Jewishnot grpmax-eligible	0.23%	435
African / African-American	0.125%	798
Middle Eastern	0.0497%	2,013
South Asian	0.0143%	7,007
East Asian	0.00223%	44,884

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CRIP1
Protein: p.Cys52Phe
Coding: c.155G>T
MANE Select: NM_001311
dbSNP: rs7824
Type: single nucleotide variant
Location: chr14:105488350 (GRCh38)
Gene constraint: LOEUF 1.447 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.41
Residue 52: the lim zinc-binding domain

Full CRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRIP1 p.Ala58Pro Uncertain significance ★ ⚠ same type
CRIP1 p.Arg16Thr Uncertain significance ★ ⚠ same type
CRIP1 p.Arg26Gln Uncertain significance ★ ⚠ same type
CRIP1 p.Arg26Trp Uncertain significance ★ ⚠ same type
CRIP1 p.Arg68Gln Uncertain significance ★ same type
CRIP1 p.Arg68Gly Uncertain significance ★ ⚠ same type
CRIP1 p.Arg68Pro Uncertain significance ★ ⚠ same type
CRIP1 p.Arg68Trp 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/crip1-p-cys52phe (accessed [today's date]).

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