Is FDFT1 p.Phe103Cys (c.308T>G) pathogenic?

FDFT1 p.Phe103Cys (c.308T>G) is classified Uncertain significance in FDFT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.1072); Ultra-rare (popmax 0.0493%, mid).

How common is FDFT1 p.Phe103Cys (c.308T>G) in the general population?

FDFT1 p.Phe103Cys (c.308T>G) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about FDFT1 p.Phe103Cys (c.308T>G)?

AlphaMissense predicts likely benign (score 0.1072) — an in-silico prediction, not a clinical call.

FDFT1 p.Phe103Cys

c.308T>G · rs368071016 · VCV2247681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1072 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1072	likely benign
REVEL	0.515	indeterminate
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.26	acceptor loss, 15 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.6	GERP -0.49, phastCons 1
Regional constraint	o/e 1.77	unconstrained · MANE · 36 kb · p 1.6e-69 · regional, not allelic
Overall
CADD	23.6	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.000682% 11/1,614,078 alleles · ultra-rare exomes 10/1,461,872 · genomes 1/152,206 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
East Asian	0.00445%	22,451
African / African-American	0.00133%	74,930
European (non-Finnish)	0.000424%	236,005

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.Phe103Cys
Coding: c.308T>G
MANE Select: NM_004462
dbSNP: rs368071016
Type: single nucleotide variant
Location: chr8:11809777 (GRCh38)
Gene constraint: LOEUF 1.764 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.14 · 32 PDB
Residue 103: an α-helix

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

Similar variants

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
FDFT1 c.100-179C>G Likely benign ★★ 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-phe103cys (accessed [today's date]).

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