Is FTCD p.Ile199Met (c.597C>G) pathogenic?

FTCD p.Ile199Met (c.597C>G) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-16). AlphaMissense: likely benign (0.1835); Very rare (popmax 0.000763%, nfe).

How common is FTCD p.Ile199Met (c.597C>G) in the general population?

FTCD p.Ile199Met (c.597C>G) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about FTCD p.Ile199Met (c.597C>G)?

AlphaMissense predicts likely benign (score 0.1835) — an in-silico prediction, not a clinical call.

FTCD p.Ile199Met

c.597C>G · VCV3911879

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1835	likely benign
REVEL	0.649	pathogenic-leaning
SaProt	LLR -12.83	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.7	GERP -2.4
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	14.99	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 0.000763% European (non-Finnish) · 9/1,179,968 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,612,880 alleles · very rare exomes 5/1,460,626 · genomes 4/152,254 · joint denominator

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: FTCD
Protein: p.Ile199Met
Coding: c.597C>G
MANE Select: NM_206965
Type: single nucleotide variant
Location: chr21:46151597 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 199: the 'formiminotransferase c-subdomain' region

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

Similar variants

FTCD p.Ile199Val Uncertain significance ★★ ⚠ same residue
FTCD p.Ile199= Likely benign ★★ same residue
FTCD p.Arg255Ter Pathogenic ★★ same type
FTCD p.Arg71Ter Pathogenic/Likely pathogenic ★★ same type
FTCD p.Leu536Ter Pathogenic/Likely pathogenic ★★ same type
FTCD p.Ala108Thr Uncertain significance ★★ ⚠ same type
FTCD p.Ala159Val Uncertain significance ★★ ⚠ same type
FTCD p.Ala352Val 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/ftcd-p-ile199met (accessed [today's date]).

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