Is CARF p.Met513Val (c.1537A>G) pathogenic?

CARF p.Met513Val (c.1537A>G) is classified Likely benign in CARF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.037); Very rare (popmax 0.00611%, nfe).

How common is CARF p.Met513Val (c.1537A>G) in the general population?

CARF p.Met513Val (c.1537A>G) is very rare (popmax 0.00611%, nfe) (gnomAD).

What do computational predictors say about CARF p.Met513Val (c.1537A>G)?

AlphaMissense predicts likely benign (score 0.037) — an in-silico prediction, not a clinical call.

CARF p.Met513Val

c.1537A>G · VCV3485014

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.037 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00611%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.037	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -4.11	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 8.5	GERP 0.61, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 42 kb · p 0.0037 · regional, not allelic
Overall
CADD	17.49	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 0.00611% European (non-Finnish) · 72/1,178,936 alleles

Filtering AF 0.00495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00465% 75/1,612,396 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00611%	16,374
Remaining individualsnot grpmax-eligible	0.0032%	31,214
Admixed American	0.00167%	59,926

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.Met513Val
Coding: c.1537A>G
MANE Select: NM_024744
Type: single nucleotide variant
Location: chr2:202977311 (GRCh38)
Gene constraint: LOEUF 0.782 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.59

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-met513val (accessed [today's date]).

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