Is FTCD p.Arg382His (c.1145G>A) pathogenic?

FTCD p.Arg382His (c.1145G>A) is classified Uncertain significance in FTCD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.1315); Very rare (popmax 0.00476%, sas); Associated with Inborn genetic diseases.

What condition is associated with FTCD p.Arg382His (c.1145G>A)?

FTCD p.Arg382His (c.1145G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FTCD p.Arg382His (c.1145G>A) in the general population?

FTCD p.Arg382His (c.1145G>A) is very rare (popmax 0.00476%, sas) (gnomAD).

What do computational predictors say about FTCD p.Arg382His (c.1145G>A)?

AlphaMissense predicts likely benign (score 0.1315) — an in-silico prediction, not a clinical call.

FTCD p.Arg382His

c.1145G>A · rs757496597 · VCV2557111

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1315 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00476%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1315	likely benign
REVEL	0.354	indeterminate
SaProt	LLR -9.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.1	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 19 kb · p 0.00063 · regional, not allelic
Overall
CADD	31.0	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 0.00476% South Asian · 4/84,000 alleles

Filtering AF 0.00161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000949%

Overall 0.000582% 9/1,546,952 alleles · very rare exomes 8/1,394,996 · genomes 1/151,956 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00476%	21,000
Admixed American	0.00196%	50,978
Remaining individualsnot grpmax-eligible	0.00167%	59,966
European (non-Finnish)	0.000262%	381,875

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.Arg382His
Coding: c.1145G>A
MANE Select: NM_206965
dbSNP: rs757496597
Type: single nucleotide variant
Location: chr21:46145532 (GRCh38)
Gene constraint: LOEUF 1.61 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.30
Residue 382: the 'cyclodeaminase/cyclohydrolase' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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FTCD p.Ala352Val Uncertain significance ★★ ⚠ same condition
FTCD p.Ala361Val Uncertain significance ★★ same condition
FTCD p.Ala418Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala455Thr Uncertain significance ★★ ⚠ same condition
FTCD p.Ala455Val Uncertain significance ★★ ⚠ same condition

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-arg382his (accessed [today's date]).

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