Is FADS2 p.Arg73Cys (c.217C>T) pathogenic?

FADS2 p.Arg73Cys (c.217C>T) is classified Uncertain significance in FADS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: likely benign (0.1014); Very rare (popmax 0.00775%, sas).

How common is FADS2 p.Arg73Cys (c.217C>T) in the general population?

FADS2 p.Arg73Cys (c.217C>T) is very rare (popmax 0.00775%, sas) (gnomAD).

What do computational predictors say about FADS2 p.Arg73Cys (c.217C>T)?

AlphaMissense predicts likely benign (score 0.1014) — an in-silico prediction, not a clinical call.

FADS2 p.Arg73Cys

c.217C>T · rs769154001 · VCV2387318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1014 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00775%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1014	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.34	GERP -1.6, phastCons 0.001
Regional constraint	o/e 0.57	unconstrained · MANE · 9,412 bp · p 7.5e-06 · regional, not allelic
Overall
CADD	19.05	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 0.00775% South Asian · 7/90,364 alleles

Filtering AF 0.00361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00256%

Overall 0.00199% 32/1,611,104 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00775%	12,909
Admixed American	0.0067%	14,935
Remaining individualsnot grpmax-eligible	0.00481%	20,784
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,520
European (non-Finnish)	0.00136%	73,668
African / African-American	0.00134%	74,824

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: FADS2
Protein: p.Arg73Cys
Coding: c.217C>T
MANE Select: NM_004265
dbSNP: rs769154001
Type: single nucleotide variant
Location: chr11:61837787 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 95.39
Residue 73: the cytochrome b5 heme-binding domain

Full FADS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FADS2 p.His221= Benign ★★ same type
FADS2 p.Ala115Val Uncertain significance ★ ⚠ same type
FADS2 p.Ala408Ser Uncertain significance ★ ⚠ same type
FADS2 p.Arg14Cys Uncertain significance ★ ⚠ same type
FADS2 p.Arg353His Uncertain significance ★ ⚠ same type
FADS2 p.Arg58Gln Uncertain significance ★ ⚠ same type
FADS2 p.Asn156His Uncertain significance ★ ⚠ same type
FADS2 p.Asn234Asp 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/fads2-p-arg73cys (accessed [today's date]).

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