Is MDFIC p.Ser60Phe (c.179C>T) pathogenic?

MDFIC p.Ser60Phe (c.179C>T) is classified Likely benign in MDFIC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-12-19). AlphaMissense: likely benign (0.1098); Rare (popmax 0.59%, afr).

How common is MDFIC p.Ser60Phe (c.179C>T) in the general population?

MDFIC p.Ser60Phe (c.179C>T) is rare (popmax 0.59%, afr) (gnomAD).

What do computational predictors say about MDFIC p.Ser60Phe (c.179C>T)?

AlphaMissense predicts likely benign (score 0.1098) — an in-silico prediction, not a clinical call.

MDFIC p.Ser60Phe

c.179C>T · rs145872153 · VCV724631

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1098 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.59%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1098	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -8.57	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 1.4	GERP 1.1, phastCons 0.008
Regional constraint	o/e 1.12	unconstrained · MANE · 93 kb · p 0.027 · regional, not allelic
Overall
CADD	18.82	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 0.59% African / African-American · 440/74,626 alleles

Filtering AF 0.544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.526%

Overall 0.0314% 503/1,604,188 alleles · rare exomes 257/1,451,970 · genomes 246/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.59%	170
Admixed American	0.0594%	1,684
Remaining individualsnot grpmax-eligible	0.0322%	3,101
South Asian	0.00112%	89,136
European (non-Finnish)	0.000596%	167,855

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: MDFIC
Protein: p.Ser60Phe
Coding: c.179C>T
MANE Select: NM_001166345
dbSNP: rs145872153
Type: single nucleotide variant
Location: chr7:114942359 (GRCh38)
Gene constraint: LOEUF 1.501 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.05 · 5 PDB
Residue 60: the 'disordered' region

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

Similar variants

MDFIC p.Phe244Leu Uncertain significance ★★ ⚠ same type
MDFIC p.Gly116Arg Likely benign ★★ same type
MDFIC p.Ser66= Likely benign ★★ same type
MDFIC c.-188G>C Uncertain significance ★ same type
MDFIC c.-246C>T Uncertain significance ★ same type
MDFIC c.-24G>T Uncertain significance ★ same type
MDFIC c.-269T>A Uncertain significance ★ same type
MDFIC c.-303G>A 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/mdfic-p-ser60phe (accessed [today's date]).

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