Is CARF p.Thr623Ser (c.1867A>T) pathogenic?

CARF p.Thr623Ser (c.1867A>T) is classified Uncertain significance in CARF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: likely benign (0.0886); Very rare (popmax 0.00446%, eas).

How common is CARF p.Thr623Ser (c.1867A>T) in the general population?

CARF p.Thr623Ser (c.1867A>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CARF p.Thr623Ser (c.1867A>T)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

CARF p.Thr623Ser

c.1867A>T · rs1369939183 · VCV3137356

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -5.55	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 4	GERP 1.6, phastCons 0.99
Regional constraint	o/e 0.90	unconstrained · MANE · 42 kb · p 0.0037 · regional, not allelic
Overall
CADD	16.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,864 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000137% 2/1,461,840 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: CARF
Protein: p.Thr623Ser
Coding: c.1867A>T
MANE Select: NM_024744
dbSNP: rs1369939183
Type: single nucleotide variant
Location: chr2:202982249 (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-thr623ser (accessed [today's date]).

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