Is FDFT1 p.His381Pro (c.1142A>C) pathogenic?

FDFT1 p.His381Pro (c.1142A>C) is classified Uncertain significance in FDFT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-11). AlphaMissense: likely benign (0.1022); Very rare (popmax 0.00886%, sas).

How common is FDFT1 p.His381Pro (c.1142A>C) in the general population?

FDFT1 p.His381Pro (c.1142A>C) is very rare (popmax 0.00886%, sas) (gnomAD).

What do computational predictors say about FDFT1 p.His381Pro (c.1142A>C)?

AlphaMissense predicts likely benign (score 0.1022) — an in-silico prediction, not a clinical call.

FDFT1 p.His381Pro

c.1142A>C · rs753067078 · VCV2306274

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1022 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00886%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1022	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -5.45	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 1.77	unconstrained · MANE · 36 kb · p 1.6e-69 · regional, not allelic
Overall
CADD	25.3	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 0.00886% South Asian · 8/90,246 alleles

Filtering AF 0.0044% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00315%

Overall 0.00268% 43/1,606,914 alleles · very rare exomes 38/1,454,780 · genomes 5/152,134 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00886%	11,281
Remaining individualsnot grpmax-eligible	0.00643%	15,543
African / African-American	0.00268%	37,382
European (non-Finnish)	0.00247%	40,540

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: FDFT1
Protein: p.His381Pro
Coding: c.1142A>C
MANE Select: NM_004462
dbSNP: rs753067078
Type: single nucleotide variant
Location: chr8:11838497 (GRCh38)
Gene constraint: LOEUF 1.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.14 · 32 PDB

Full FDFT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FDFT1 p.His381Gln Uncertain significance ★ ⚠ same residue
FDFT1 c.100-85G>C Uncertain significance ★★ same type
FDFT1 p.Ala333Ser Uncertain significance ★★ ⚠ same type
FDFT1 p.Asn265Ser Uncertain significance ★★ ⚠ same type
FDFT1 p.Gly151Asp Uncertain significance ★★ ⚠ same type
FDFT1 p.Ile252Thr Uncertain significance ★★ ⚠ same type
FDFT1 p.Phe210Leu Uncertain significance ★★ ⚠ same type
FDFT1 p.Ser102Cys 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/fdft1-p-his381pro (accessed [today's date]).

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