Is CARF p.Pro587Leu (c.1760C>T) pathogenic?

CARF p.Pro587Leu (c.1760C>T) is classified Benign in CARF (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-24). AlphaMissense: likely benign (0.0648); Low-frequency (popmax 4.13%, eas).

How common is CARF p.Pro587Leu (c.1760C>T) in the general population?

CARF p.Pro587Leu (c.1760C>T) is low-frequency (popmax 4.13%, eas) (gnomAD).

What do computational predictors say about CARF p.Pro587Leu (c.1760C>T)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

CARF p.Pro587Leu

c.1760C>T · rs75249727 · VCV721243

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.13%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0648	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -5.54	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 2.2	GERP 0.58, phastCons 0.042
Regional constraint	o/e 0.90	unconstrained · MANE · 42 kb · p 0.0037 · regional, not allelic
Overall
CADD	13.85	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 4.13% East Asian · 1,851/44,872 alleles

Filtering AF 3.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.91%

Overall 0.136% 2,190/1,614,048 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	4.13%	24
Remaining individualsnot grpmax-eligible	0.24%	417
South Asian	0.11%	911
Admixed American	0.045%	2,223
African / African-American	0.036%	2,779
European (non-Finnish)	0.00288%	34,704
Finnishnot grpmax-eligible	0.00156%	64,034

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: CARF
Protein: p.Pro587Leu
Coding: c.1760C>T
MANE Select: NM_024744
dbSNP: rs75249727
Type: single nucleotide variant
Location: chr2:202982142 (GRCh38)
Gene constraint: LOEUF 0.782 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.59
Residue 587: the 'disordered' region

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

Similar variants

CARF p.Gln640Pro Uncertain significance ★★ ⚠ same type
CARF c.*377G>A Benign ★★ same type
CARF p.Pro108Ser Likely benign ★★ same type
CARF p.Pro454= Benign ★★ same type
CARF p.Thr725Ala Benign ★★ same type
CARF p.Val157Ala Likely benign ★★ same type
CARF p.Ala629Val Uncertain significance ★ ⚠ same type
CARF p.Arg142Trp 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/carf-p-pro587leu (accessed [today's date]).

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