Is FTCD p.Arg208His (c.623G>A) pathogenic?

FTCD p.Arg208His (c.623G>A) is classified Conflicting classifications of pathogenicity in FTCD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-02). AlphaMissense: likely benign (0.2148); Rare (popmax 0.53%, eas); Associated with formiminoglutamic aciduria.

What condition is associated with FTCD p.Arg208His (c.623G>A)?

FTCD p.Arg208His (c.623G>A) is associated with formiminoglutamic aciduria (ClinVar).

How common is FTCD p.Arg208His (c.623G>A) in the general population?

FTCD p.Arg208His (c.623G>A) is rare (popmax 0.53%, eas) (gnomAD).

How is Formiminoglutamic aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FTCD p.Arg208His (c.623G>A)?

AlphaMissense predicts likely benign (score 0.2148) — an in-silico prediction, not a clinical call.

FTCD p.Arg208His

c.623G>A · rs199508525 · VCV1306230

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2148 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.53%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

formiminoglutamic aciduria

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2148	likely benign
REVEL	0.807	moderately pathogenic-leaning
SaProt	LLR -7.47	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.3	GERP 1.2, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	33.0	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 0.53% East Asian · 238/44,870 alleles

Filtering AF 0.475% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.454%

Overall 0.0177% 286/1,612,478 alleles · rare exomes 241/1,460,106 · genomes 45/152,372 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.53%	189
Remaining individualsnot grpmax-eligible	0.0224%	4,462
South Asian	0.0121%	8,280
Admixed American	0.00333%	30,016
European (non-Finnish)	0.00178%	56,172

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.Arg208His
Coding: c.623G>A
MANE Select: NM_206965
dbSNP: rs199508525
Type: single nucleotide variant
Location: chr21:46151571 (GRCh38)

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

Disease context

formiminoglutamic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Formiminoglutamic aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

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-arg208his (accessed [today's date]).

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