Is CARF p.Val157Ala (c.470T>C) pathogenic?

CARF p.Val157Ala (c.470T>C) is classified Likely benign in CARF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-09). AlphaMissense: likely benign (0.1214); Rare (popmax 0.274%, afr).

How common is CARF p.Val157Ala (c.470T>C) in the general population?

CARF p.Val157Ala (c.470T>C) is rare (popmax 0.274%, afr) (gnomAD).

What do computational predictors say about CARF p.Val157Ala (c.470T>C)?

AlphaMissense predicts likely benign (score 0.1214) — an in-silico prediction, not a clinical call.

CARF p.Val157Ala

c.470T>C · rs35438756 · VCV785023

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1214 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.274%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1214	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.83	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 0.026, phastCons 0.49
Regional constraint	o/e 0.90	unconstrained · MANE · 42 kb · p 0.0037 · regional, not allelic
Overall
CADD	14.83	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 0.274% African / African-American · 205/74,926 alleles

Filtering AF 0.243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.231%

Overall 0.0164% 265/1,612,522 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.274%	365
Remaining individualsnot grpmax-eligible	0.0704%	1,419
Admixed American	0.0218%	4,595
Middle Eastern	0.0165%	6,058
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,572
European (non-Finnish)	8.48e-05%	1,179,362

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.Val157Ala
Coding: c.470T>C
MANE Select: NM_024744
dbSNP: rs35438756
Type: single nucleotide variant
Location: chr2:202954047 (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.Val157Leu Uncertain significance ★ ⚠ same residue
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.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-val157ala (accessed [today's date]).

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